Full download test bank at ebook ebookmass.

com

Gray's Anatomy: The Anatomical

Basis of Clinical Practice 42th
Edition Susan Stranding

CLICK LINK TO DOWLOAD

https://ebookmass.com/product/grays-anatomy-
the-anatomical-basis-of-clinical-
practice-42th-edition-susan-stranding/

ebookmass.com
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Burns & Grove's The Practice of Nursing Research 9th

Edition Jennifer R. Gray

https://ebookmass.com/product/burns-groves-the-practice-of-
nursing-research-9th-edition-jennifer-r-gray/

Clinical Anatomy of the Spine, Spinal Cord, and ANS 3rd

Edition

https://ebookmass.com/product/clinical-anatomy-of-the-spine-
spinal-cord-and-ans-3rd-edition/

Respiratory Care Anatomy and Physiology E Book:

Foundations for Clinical Practice 4th Edition, (Ebook
PDF)

https://ebookmass.com/product/respiratory-care-anatomy-and-
physiology-e-book-foundations-for-clinical-practice-4th-edition-
ebook-pdf/

Clinical Atlas of Human Anatomy 8th Edition Peter H.

Abrahams

https://ebookmass.com/product/clinical-atlas-of-human-
anatomy-8th-edition-peter-h-abrahams/
Clinical Research for the Doctor of Nursing Practice

https://ebookmass.com/product/clinical-research-for-the-doctor-
of-nursing-practice/

The Practice of Clinical Echocardiography 5th Edition

Catherine M. Otto

https://ebookmass.com/product/the-practice-of-clinical-
echocardiography-5th-edition-catherine-m-otto/

Netter's Clinical Anatomy E-Book 4th ed Edition Hansen

https://ebookmass.com/product/netters-clinical-anatomy-e-
book-4th-ed-edition-hansen/

The Lost Art of Connecting Susan Mcpherson [Susan

Mcpherson]

https://ebookmass.com/product/the-lost-art-of-connecting-susan-
mcpherson-susan-mcpherson-2/

The Lost Art of Connecting Susan Mcpherson [Susan

Mcpherson]

https://ebookmass.com/product/the-lost-art-of-connecting-susan-
mcpherson-susan-mcpherson/
Publisher: Jeremy Bowes
Senior Content Development Specialist: Trinity Hutton
Deputy Content Development Manager: Joanne Scott
Project Managers: Julie Taylor, Joanna Souch
Production Manager: Deena Burgess
Designer: Amy Buxton
Illustration Manager: Paula Catalano
Illustrators: Antbits (Paul Richardson, Richard Tibbitts), Edanart (Ethan Danielson)
Copyeditor: Elaine Leek
Proofreaders: Glenys Norquay and Susan Stuart
Indexer: Jan Ross, Merrall-Ross International
Marketing Manager: Michele Milano
 Anatomy
GRAY’S
THE ANATOMICAL BASIS
OF CLINICAL PRACTICE
Editor-in-Chief
Susan Standring MBE, PhD, DSc, FKC, Hon FAS, Hon FRCS
Emeritus Professor of Anatomy
King’s College London
London, UK

SECTION EDITORS Alistair Ross MB, FRCS Caroline B Wigley BSc, PhD
Consultant Orthopaedic Surgeon Retired Preclinical Tutor
Neel Anand MD The Bath Clinic University of Exeter Medical
Clinical Professor of Surgery Bath, UK School
Director, Spine Trauma, Exeter, UK
Minimally Invasive Spine
Surgery
R Shane Tubbs MS, PA-C, PhD
Spine Center
Professor Stephanie J Woodley PhD,
Departments of Neurosurgery, MSc, BPhty
Cedars Sinai Medical Center
Neurology and Structural and Associate Professor
Los Angeles, CA, USA
Cellular Biology Department of Anatomy
Tulane University School of School of Biomedical Sciences
Marco Catani MD, PhD Medicine University of Otago
Professor of Neuroanatomy & New Orleans, LA, USA Dunedin, New Zealand
Psychiatry Professor of Human Gross and
NatBrainLab Developmental Anatomy
Department of Forensic and Department of Anatomical
SPECIAL EDITORS
Neurodevelopmental Sciences Sciences
Institute of Psychiatry, Surface Anatomy
St George’s University
Psychology and Neuroscience Grenada, West Indies Richard Tunstall BMedSci,
King’s College London Faculty PhD, FHEA
London, UK National Skull Base Foundation
Thousand Oaks, CA, USA Imaging
Patricia Collins BSc, PhD, FHEA Faculty
Emeritus Professor of Anatomy Department of Neurosurgery
Tom Turmezei MPhil, MA,
AECC University College and Ochsner Neuroscience BMBCh, PhD, FRCR
Bournemouth, UK Institute Consultant Radiologist
Ochsner Health System Norfolk and Norwich
Alan R Crossman BSc, PhD, New Orleans, LA, USA University Hospital
Norwich, UK
DSc
Honorary Senior Lecturer
Emeritus Professor of Anatomy Richard Tunstall BMedSci, University of East Anglia, UK
The University of Manchester PhD, FHEA Royal College of Radiologists
Manchester, UK Professor of Clinical Anatomy 2020 Roentgen Professor
and Imaging
Michael Gleeson MD, FRCS, Warwick Medical School
University of Warwick, UK Cell and Tissue Microstructure
FRACS, FDS
Professor of Skull Base Surgery Professor of Clinical Anatomy Caroline B Wigley BSc, PhD
University College London West Midlands Surgical
The National Hospital for Training Centre
Neurology and Neurosurgery UHCW NHS Trust
London, UK Coventry, UK
Applied Surgical Anatomy Lead
Royal College of Surgeons
London, UK

Forty-Second Edition
© 2021, Elsevier Limited. All rights reserved.

Forty-first edition published 2016 Get the most out of your Gray’s Anatomy
Forty-Second Edition
Fortieth edition published 2008

First edition JW Parker & Son 1858 Included in your purchase is a rich variety of BONUS electronic
content, to supplement and enhance the printed book.
No part of this publication may be reproduced or transmitted in any
form or by any means, electronic or mechanical, including photocopy- Look out for this icon , indicating where there is related further
ing, recording, or any information storage and retrieval system, without electronic text, images, tables, labelled imaging or video material.
permission in writing from the publisher. Details on how to seek per-
mission, further information about the Publisher’s permissions policies In addition, you can access 21 ‘Gray’s Commentaries’: especially
and our arrangements with organizations such as the Copyright written (electronic only) articles on new and emerging topics related to
Clearance Center and the Copyright Licensing Agency, can be found at anatomy. This icon highlights where one relates directly to a topic in
our website: www.elsevier.com/permissions. the printed book. S Chapters 80 and 81 (electronic only) contain
descriptions of the systematic anatomy of the peripheral nervous
This book and the individual contributions contained in it are protected
under copyright by the Publisher (other than as may be noted herein). system and vascular system, respectively.

For an extended historical bibliography, all references from the thirty-

Notices
eighth edition (which includes all references cited in earlier editions, up
Practitioners and researchers must always rely on their own experience
and knowledge in evaluating and using any information, methods, to and including the thirty-eighth edition) are also available in the
compounds or experiments described herein. Because of rapid advances e-book that accompanies Gray’s Anatomy.
in the medical sciences, in particular, independent verification of diag- Don’t miss out on any of this additional electronic content – see the
noses and drug dosages should be made. To the fullest extent of the
law, no responsibility is assumed by Elsevier, authors, editors or con- inside front cover for your access instructions.
tributors for any injury and/or damage to persons or property as a
matter of products liability, negligence or otherwise, or from any use or
operation of any methods, products, instructions, or ideas contained in
the material herein.

Although all advertising material is expected to conform to ethical

(medical) standards, inclusion in this publication does not constitute
a guarantee or endorsement of the quality or the value of such product
or the claims made of it by its manufacturer.

ISBN: 978-0-7020-7705-0 COVER IMAGE

9780702077067
The cover image for this edition is a cinematically rendered 3D
Printed in China reconstruction of a normal heart from a contrast-enhanced computed
tomography (CT) coronary angiography study performed at the Royal
Last digit is the print number: 9 8 7 6 5 4 3 2 1 Papworth Hospital, Cambridge, UK. Image reconstruction and post-
processing was performed on a SIEMENS syngo.via Frontier workstation
by Dr Julia Sun (Clinical Fellow in Radiology, Royal Papworth Hospital) with
further editing by Dr Jonathan Weir-McCall (Honorary Consultant
Radiologist, Royal Papworth Hospital) and Dr Tom Turmezei (Consultant
Radiologist, Norfolk and Norwich University Hospital).
PREFACE

A common definition of a preface is that it is ‘an introduction to a book, in Gray’s Anatomy was described as ‘stultifying’ (Tansey 1995).1
typically stating its subject, scope or aims’. It is often the only place where The text of the 42nd edition of Gray’s Anatomy is almost entirely
an author or editor speaks directly to their readership, and in this Terminologia Anatomica 2-compliant.2 However, on occasion the pre-
respect, a preface is akin to an actor breaking the conceptual ‘fourth ferred term that is used is a synonym that may not be TA2-compliant:
wall’ in the theatre or on film. In the Preface to the first edition in 1858 it has been chosen either because it is the agreed term in the relevant
Henry Gray wrote that ‘This Work is intended to furnish the Student and clinical consensus document or, as my editors frequently remind me,
Practitioner with an accurate view of the Anatomy of the Human Body, and because it enjoys widespread clinical usage, whereas the TA-compliant
more especially the application of this science to Practical Surgery’. Subsequent term does not.3 Wherever this occurs, all terms are included at first
editions of Gray’s Anatomy not only upheld that intention, but devel- meeting, with synonyms in parentheses.
oped it, in order to embrace and engage a wider readership. The use of eponyms is contentious: detractors argue that they are
The first two editors to succeed Gray were Timothy Holmes (1863– inherently inaccurate, non-scientific and often undeserved, while pro-
1880) and Thomas Pickering Pick (1883–1905). They both wondered ponents point out that eponyms are deeply embedded in the anatomi-
in their Prefaces whether it was appropriate to include findings from cal and clinical literature and that they remind us of the giants on whose
the burgeoning discipline of anatomical science in a book intended shoulders we stand. On balance, I believe that Gray’s Anatomy is an
specifically for students of surgery: ‘so long as the Examining Bodies do appropriate repository for anatomical eponyms: they are cited in paren-
not exact a knowledge of this branch of science as a necessary part of Medical theses on first usage of a preferred term in the text and an updated list
Education, it would be unwise to encumber the pages of a work designed of eponyms is available in the e-book for reference purposes. I recognize
specifically for students with matter which, however interesting and valuable the irony in the exclusion of Henry Vandyke Carter’s name from the
in itself, could hardly be regarded as essential’ (Holmes, 3rd edition, 1863). eponymous title of Gray’s Anatomy, particularly since Carter’s drawings
Pickering Pick pointed out that microscopical anatomy had been invariably attracted praise: ‘those excellent images which have … contrib-
revised in the 10th edition ‘in order to keep pace with the ever-increasing uted so materially to smooth the thorny path of the student of human anatomy’
activity of research in the branch of the science of Anatomy’ (1883), and (Carter’s obituary, BMJ May 15 1897); ‘The splendid illustrations in Gray
while not intending the 13th edition for the ‘scientific anatomist’, he have long been known as the most effective and intelligible presentations of
was anxious not ‘to disparage, for an instant, the study of Philosophical or anatomical structure ever produced …’ (Preface to the American 15th
Scientific Anatomy’ (1893). edition, 1901).
Future editions slowly assimilated findings in the fields of cell As a general rule, the orientation of diagrams and photographs
biology, embryology, neuroanatomy and imaging: just as the discipline throughout the book has been standardized to show the left side of the
it describes has evolved, so a book originally intended for students of body, irrespective of whether a lateral or medial view is presented.
surgery has morphed into the great reference book that is published Transverse sections have been drawn from below to facilitate compari-
today. Our current view of the detailed internal landscape of the body, son with axial clinical images: the conventional ‘top down’ orientation
from molecular to whole body and from conception onwards, owes has been retained in diagrams in Section 3 (neuroanatomy).
much to the enormous technological advances that have taken place in Clinicopathological examples have been selected where the pathology
the last half century. Our ‘anatomical gaze’ has been enlightened by is either a direct result, or a consequence, of the anatomy, or where the
progress in bioinformatics, molecular biology, experimental genetics, anatomical features are instrumental in the diagnosis/treatment/man-
light and electron microscopy, diagnostic imaging (including X-rays, agement of the condition. Unless otherwise indicated, the photomicro-
magnetic resonance imaging, computed tomography and ultrasonogra- graphs illustrate human histology and embryology.
phy), and the use of ‘soft’ perfusion techniques and frozen–thawed, In the Preface to the 39th edition I explained that the editorial team
unembalmed cadavers for dissection-based studies and surgical train- had decided that, in order to provide the greatest benefit to clinicians,
ing. That gaze is not only informed by, but also informs, the design and Gray’s Anatomy would better mirror their daily practice if anatomy was
negotiation of minimally invasive surgical access routes to structures described in the way that they use it, i.e. regionally. That said, including
and regions that were once regarded as inaccessible ‘tiger territories’. regional and systematic descriptions of topographical anatomy has
The momentum created by these changes powered the radical modern- remained my goal and I am therefore delighted that the anatomy of the
izing revisions seen in the 36th to 38th editions under the editorship nervous and vascular and lymphatic systems is included in the online
of Roger Warwick and Peter Williams: ‘The discipline of Anatomy has version of the 42nd edition (in Chapters 80 and 81).
changed out of all recognition because it is no longer just “Descriptive and Neel Anand, Marco Catani, Pat Collins, Alan Crossman, Michael
Applied”’ (Editorial team, Preface to the 38th edition, 1995), and has Gleeson, Alistair Ross, Shane Tubbs, Richard Tunstall, Caroline Wigley
continued to drive subsequent editions. and Stephanie Woodley brought a wealth of scholarship and experience
Terminological disputes have long entertained anatomists: ‘one cynic as anatomists, cell biologists, research scientists, educators and clini-
has commented that anatomists would rather use each other’s toothbrushes cians to their roles as Section Editors. They recognize that a knowledge
than employ their terminology’ (Tansey 1995).1 Henry Gray’s anatomical of clinically relevant and evidence-based anatomy is essential for safe
terminology in the first edition can be little different from the language and effective clinical practice across all specialisms. It is with great
he used when teaching and operating at St George’s Hospital: his words pleasure that I thank them for their dedication and enthusiastic support,
were written long before the publication of the Basle Nomina Anatomica both in selecting and interacting with the authors in their Sections and
(BNA) in 1895. The exasperated comments of TB Johnston, in his in meeting Elsevier’s deadlines, despite the ever-increasing demands on
Preface to the 25th edition, have a familiar ring almost 90 years later: their time from their university and/or clinical managers. Richard
‘It is my earnest hope that before another edition of this work is published, the
question of terminology will have been settled and an unproductive subject will
have ceased to occupy attention’ (Johnston 1932). These hopes have not been
entirely satisfied. An early attempt to reconcile differing terminologies 2
Terminologia Anatomica 2, 2019 https://fipat.library.dal.ca/TA2/; Terminologia
Histologica, Philadelphia: Lippincott Williams & Wilkins, 2008; Terminologia
Embryologica, 2017 https://FIPAT.library.dal.ca; Terminologia Neuroanatomica,
2017 https://FIPAT.library.dal.ca.
3
Jeppson PC, Balgobin S, Washington BB et al 2018 Recommended standardized ter-
1
Tansey EM 1995 A brief history of Gray’s Anatomy. In Gray’s Anatomy 38th ed minology of the anterior female pelvis based on a structured medical literature
(Williams PL et al eds). pp. xvii–xx. Edinburgh: Churchill Livingstone. review. Am J Obstet Gynecol 219:26–39. ix
 Preface

Tunstall and Caroline Wigley also worked closely with many authors I offer my sincere thanks to the editorial team at Elsevier, under the
to update the text and artworks for evidence-based surface anatomy and leadership of Jeremy Bowes, for their guidance, professionalism, good
microstructure, respectively, across Sections 3 to 9. Tom Turmezei has humour and unfailing support at all times. I particularly thank Trinity
been an enthusiastic ‘go to’ editor for sourcing images throughout the Hutton, Joanna Souch, Julie Taylor and Elaine Leek, for being at the
book: Tom and his team have produced a superb collection of addi- end of a phone or available by e-mail whenever I needed advice or
tional labelled images (see Bonus imaging collection). Owen Arthurs support. I thank the artists who have worked to produce new artworks
and his colleagues at Great Ormond Street Hospital provided microCT under Richard Tibbitts’ leadership, continuing the tradition of Henry
images for Section 2 (Embryogenesis and development). Over a Vandyke Carter, the first great illustrator of Gray’s Anatomy.
hundred highly experienced clinicians and anatomists have contributed I dedicate my work on this edition of Gray’s Anatomy to my daugh-
new text and/or artworks, original micrographs or other images to ters, Helen and Caroline.
individual chapters and I thank them all for their input – as ever, it has Susan Standring
been an enriching experience to read their revisions. February 2020

PROFESSOR EMERITUS KARL ZILLES (1944–2020)

It was with great sadness that we learned that Professor Emeritus Karl architecture of each area under different conditions (Zilles et al 1986,
Zilles, who co-authored the updated chapter on the cerebral hemi- Zilles and Palomero-Gallagher 2017).
spheres (Chapter 32), died while the proofs of this edition of Gray’s In the last 15 years, Karl Zilles and his collaborators introduced an
Anatomy were being finalized. He was an outstanding neuroscientist and ultra-high resolution method for axon and white matter fibre visualiza-
‘…his dedication, rigor, and scientific approaches have been transformative tion based on polarized light imaging (Axer et al 2011). Future develop-
in the field of neuroanatomy…’ (Zaborszky 2020). The quantitative his- ments and applications of this technique will offer an invaluable tool
tological methods that he developed have played a significant role in with which to describe the organization of neural connections in the
bridging the gap between classical post-mortem neuroanatomy and brain and to validate current descriptions of white matter tracts based
neuroimaging of the living human brain. on in vivo diffusion MRI tractography.
Karl Zilles graduated in medicine from the Johann-Wolfgang-Goethe To his students, collaborators and friends, Professor Karl Zilles was
University in Frankfurt in 1971 and received a PhD in Anatomy from an inspirational and encouraging figure, always ready to converse and
the Medical School of Hannover in 1977. He became full Professor of write about neuroanatomy, history of neuroscience, epistemology, phi-
Anatomy and Neuroanatomy at the University of Cologne in 1981 and losophy and ethics: he will be deeply missed.
was Director of the prestigious Cécil and Oscar Vogt Institute for Brain
Research at Heinrich Heine University in Düsseldorf from 1991 to 2012
and the Institute of Neurosciences and Medicine at the Forschungszentrum
in Jülich from 1998 to 2012. References
During a long and highly productive career, Karl Zilles explored the
Amunts K, Schleicher A, Bürgel U, Mohlberg H, Uylings HBM, Zilles K 1999
structural, molecular and functional organization of the marsupial, Broca’s region revisited: Cytoarchitecture and intersubject variability.
rodent, non-human primate and human cerebral cortices. Very early, he J Comp Neurol 412: 319–341.
introduced TV cameras connected to a microscope for extracting quan- Axer M, Amunts K, Grässel D, Palm C, Dammers J, Axer H, Pietrzyk U, Zilles
titative morphometric parameters from histological sections (Zilles et al K 2011 A novel approach to the human connectome: Ultra-high resolu-
1978). The realization of the existence of significant inter-individual tion mapping of fiber tracts in the brain. NeuroImage 54: 1091–1101.
differences in brain architecture led him to propose and establish the Schormann T, Dabringhaus A, Zilles K 1995 Statistics of deformations in
use of 3D cytoarchitectonic probabilistic maps of cortical areas (Amunts histology and application to improved alignment with MRI. IEEE
et al 1999, Schormann et al 1995). The rapid development of in vivo Transactions on Medical Imaging 14: 25–35.
neuroimaging methods combined with a quantitative probabilistic Zaborszky L 2020 Karl Zilles (1944–2020): a personal tribute. Brain Struct
approach to cytoarchitectonic brain mapping produced reference atlases Funct 225:1185–1187. https://doi.org/10.1007/s00429-020-02088-5.
and digital databases for the precise localization of cortical areas and Zilles K, Schleicher A, Kretschmann HJ 1978 A quantitative approach to
functions in the human brain (Zilles and Amunts 2010). cytoarchitectonics. I. The areal pattern of the cortex of Tupaia belangeri.
He developed a method for the quantitative autoradiograpical analy- Anat Embryol 153:195–212.
sis of the laminar and regional distribution of multiple transmitter Zilles K, Amunts K 2010 Centenary of Brodmann’s map – conception and
receptors. He introduced neurotransmitter fingerprints, which reflect fate. Nature Rev Neurosci 11:139–145.
the balance between different receptors and neurotransmitter systems Zilles K, Schleicher A, Rath M et al 1986 Quantitative autoradiography of trans-
that characterize each cortical area. He demonstrated that receptor fin- mitter binding sites with an image analyzer. J Neurosci Meth 18: 207–220.
gerprints differ across species and between healthy and diseased brains, Zilles K, Palomero-Gallagher N 2017 Multiple transmitter receptors in
and therefore represent a very powerful tool to study the molecular regions and layers of the human cerebral cortex. Front Neuroanat 11:78.

x
ACKNOWLEDGEMENTS

Elsevier and the Gray’s Anatomy 42nd edition editorial team would like to offer sincere thanks to the Department of
Radiology at the Norfolk and Norwich University Hospital, Norwich, UK, for their support in sourcing and prepar-
ing over 140 superb new radiological imaging figures for this edition. Guided by Imaging Editor Dr Tom Turmezei,
these include cutting-edge images that showcase the impact of radiology on anatomical education, harnessing
different modalities and image processing techniques to show living internal human anatomy in detail. In particular,
we would like to thank consultant radiologists Tariq Ali, Phyllis Mezue and Iztok Caglic; musculoskeletal radiology
clinical fellow Elliott Rees; and radiology trainees Julia Sun, Ramona-Rita Barbara, Fatma Eminaga, Amr Moussa,
Nathan Chan and Emily Pearlman.
The following images were sourced by the Department of Radiology at the Norfolk and Norwich University Hospital:
33.1B,C; 33.2B; 33.3B; 34.1C; 34.2B; 34.3B; 34.4C; 35.4C; 35.24H-L; 37.11B; 37.40B,C; 37.41; 37.45D,E; 38.14C–E;
39.6B–F; 40.2B; 41.6B; 44.5B; 44.6C; 44.7B; 44.13B–E; 46.6B,C; 46.20C; 46.23B; 46.25B,C; 46.27B,C; 46.44B;
46.45; 46.46A–C; 46.51C–G; 46.60B–D; 46.63B,C; 46.66B; 46.74; 47.1G; 48.3B–D; 48.4B–E; 48.7B–G; 49.15B;
49.22C; 49.23A,B; 49.30B; 50.13E–G; 50.16; 50.17B; 50.27B; 50.31B; 50.32B; 51.19D; 51.20A–D; 52.2B; 53.12B;
54.4C–H; 54.5B; 54.6F–O; 55.1B–E; 56.9B–E; 57.4F; 57.7BC; 57.17B; 57.21B; 57.27B; 57.46; 57.47; 57.48; 57.49;
57.50; 57.51; 57.59C; 58.3; 59.5B; 60.1B; 60.3C; 60.9C,D; 63.10B,C; 64.14A–C; 65.37A,B; 65.44C; 66.9B; 66.12;
67.10; 71.5B; 71.6B; 72.6A–D; 73.1B; 73.2D; 73.15C;76.3C; 77.2B; 77.17B; 77.24B; 77.28B; 77.43C,D; 77.48B,C;
78.6C; 78.14B; 78.24B; 79.4B; 79.8B; 79.9D,E; 79.10B; 79.15B; 79.17B; 79.19B
Elsevier and the Gray’s Anatomy 42nd edition editorial team would also like to offer sincere thanks to Mr Peter Helliwell
(Head Biomedical Scientist, Department of Cellular Pathology, Royal Cornwall Hospitals Trust, Truro, UK) for
contributing numerous high resolution photomicrographs of specially prepared histological sections of human
tissues for the 40th, 41st and 42nd editions of Gray’s Anatomy, many prepared in collaboration with the late Dr
Joseph Mathew.

xi
 CONTRIBUTORS to the forty-second edition

The editor(s) acknowledge and offer grateful thanks for the input of all contributors to previous editions, without whom this new edition would
not have been possible.

Michael A Adams BSc, PhD Eli Baron MD Kevin Gerard Byrnes MB BCh BAO, MCh,
Professor of Biomechanics, and Associate Professor of Neurosurgery MRCS, PhD
Senior Research Fellow Co-Director Spine Trauma Program Graduate Entry Medical School
Centre for Applied Anatomy Spine Surgeon University of Limerick
University of Bristol Cedars-Sinai Spine Center University Hospitals Group Limerick
Bristol, UK Los Angeles, CA, USA Dooradoyle, Ireland

Mohamad E Allaf MD Barry KB Berkovitz BDS, MSc, PhD, FDS Alison Campbell BSc (Hons), M Med Sci,
Professor of Urology Emeritus Reader in Dental Anatomy Dip RCPath
Johns Hopkins University School of King’s College London Group Director of Embryology
Medicine London, UK CARE Fertility Group
Baltimore, MD, USA Nottingham, UK
Christopher D Bernard MD
Neel Anand MD Department of Orthopedic Surgery Marco Catani MD, PhD
Clinical Professor of Surgery Mayo Clinic Professor of Neuroanatomy & Psychiatry
Director, Spine Trauma, Minimally Invasive Rochester, MN, USA NatBrainLab
Spine Surgery Department of Forensic and
Spine Center Ranjeev Singh Bhangoo MBChB (Hons), Neurodevelopmental Sciences
Cedars Sinai Medical Center FRCS (Eng), FRCS (SN) Institute of Psychiatry, Psychology and
Los Angeles, CA, USA Clinical Director of Neuroscience and Neuroscience
Consultant Neurosurgeon King’s College London
Praveen Anand MD, MRCP, FRCP Department of Neurosurgery London, UK
Professor of Clinical Neurology King’s College NHS Foundation Trust
Faculty of Medicine London, UK Carmen Cavada MD, PhD
Department of Brain Sciences Professor, Human Anatomy and Neuroscience
Head, Centre for Clinical Translation Jasneet Singh Bhullar MD, MS, FACS, Director, Chair in Neuroscience UAM-
Imperial College London, Hammersmith FASCRS Fundación Tatiana Pérez de Guzmán el
Hospital Colorectal Surgeon Bueno
London, UK UPMC Susquehanna Department of Anatomy, Histology and
Williamsport, PA, USA Neuroscience
Nihal Apaydin MD, PhD Universidad Autónoma de Madrid
Professor of Anatomy Rolfe Birch MChir, FRCPS(Glasg), FRCS(Ed), Madrid, Spain
Department of Anatomy, Faculty of FRCS(Eng)
Medicine Faculty of Medicine Paul H Chung MD
Department of Neuroscience, Institute of Imperial College London Assistant Professor of Urology
Health Sciences Hammersmith Hospital Sidney Kimmel Medical College
AU Brain Research Center London, UK Thomas Jefferson University
Ankara University Philadelphia, PA, USA
Ankara, Turkey Kelly Brown MBBS, MRCPCH
Consultant Neonatologist John Calvin Coffey BSc, B MedSci, MB,
Tipu Zahed Aziz FMedSci University Hospital Southampton NHS PhD, AFRSCI, FRCSI
Professor of Neurosurgery Foundation Trust Foundation Chair of Surgery
John Radcliffe Hospital Southampton, UK Graduate Entry Medical School
University of Oxford University of Limerick
Oxford, UK Graham J Burton MD, DSc, FMedSci University Hospitals Group Limerick
Mary Marshall and Arthur Walton Professor Dooradoyle, Ireland
Stuart Ballantyne MBChB, FRCS, FRCR of the Physiology of Reproduction
Department of Radiology Department of Physiology, Development and Patricia Collins BSc, PhD, FHEA
Gartnavel General Hospital; Neuroscience Emeritus Professor of Anatomy
Queen Elizabeth University University of Cambridge AECC University College
Hospital Cambridge, UK Bournemouth, UK
Glasgow, UK
Andrew Bush MB BS MD FHEA FRCP Gerardo Conesa Bertran MD, PhD
Winfried Banzer FRCPCH FERS FAPSR ATSF Director of the Neurosurgical Department
Institute of Sports Science Professor of Paediatrics and Paediatric Hospital de Sant Pau and Hospital del Mar
Goethe-Universität Frankfurt am Main Respirology, and Consultant Paediatric Barcelona, Spain
Germany Chest Physician
Paediatric Respiratory Medicine Claudius Conrad MD, PhD
Imperial College and Royal Brompton Department of Surgery
Harefield NHS Foundation Trust Saint Elizabeth Medical Center
London, UK Boston, MA, USA

xii
 CONTRIBUTORS

Declan Costello MA, MBBS, FRCS Quentin Fogg BSc (Hons), PhD, Simon Holmes BDS, MBBS, FDS, RCS,
(ORL-HNS) FRCPS (Glasg) FRCS
Consultant Ear Nose and Throat Surgeon Associate Professor Professor of Craniofacial Traumatology
specializing in voice disorders Department of Anatomy and Neuroscience Department of Oral and Maxillofacial Surgery
Wexham Park Hospital The University of Melbourne Royal London Hospital, Queen Mary
Slough, UK Melbourne, VIC, Australia University of London
London, UK
Alan R Crossman BSc, PhD, DSc Matthew J Forshaw MA, MSc, MB, BChir,
Emeritus Professor of Anatomy FRCS Claire Hopkins MA (Oxon), FRCS (ORLHNS),
The University of Manchester Consultant Upper Gastrointestinal and DM
Manchester, UK General Surgeon Consultant Ear, Nose and Throat Surgeon
Glasgow Royal Infirmary Guy’s and St Thomas’ Hospitals;
Craig Andrew Cunningham BSc (Hons), Glasgow, UK Professor of Rhinology
PhD, FRAI King’s College London
Senior Lecturer of Human Anatomy David Nicholas Furness BSc, PhD London, UK
Centre for Anatomy and Human Identification Professor of Cellular Neuroscience
University of Dundee School of Life Sciences Joe Iwanaga DDS, PhD
Dundee, UK Keele University Associate Professor
Newcastle-under-Lyme, UK Department of Neurosurgery
Anthony V D’Antoni MS, DC, PhD Tulane University School of Medicine
Assistant Professor of Anatomy in Radiology Donna Geddes DMU, PostGrad Dip (Sci), New Orleans, LA, USA
Division of Anatomy, Department of PhD
Radiology Professor Eric Jauniaux MD, PhD, FRCOG
Weill Cornell Medicine School of Molecular Sciences Professor in Obstetrics and Fetal Medicine
New York, NY, USA Faculty of Science EGA Institute for Women’s Health
The University of Western Australia Faculty of Population Health Sciences,
Ignacio Delgado-Martínez MD, PhD Perth, WA, Australia University College London
Department of Neurosurgery London, UK
Hospital del Mar Medical Research Institute Andrew George MBE, MA, PhD, DSc,
(IMIM) FRCPath, FHEA, FRSA, FRSB Bjarke Jensen PhD
Barcelona, Spain Emeritus Professor of Immunology Assistant Professor
Brunel University London Department of Medical Biology
Emmanuel D’Heygere MD London, UK Amsterdam University Medical Centers
Otolaryngologist Amsterdam, The Netherlands
Department of Otolaryngology Michael Gleeson MD, FRCS, FRACS, FDS
AZ Groeninge Hospital, Professor of Skull Base Surgery Mickey Karram MD
Kortrijk, Belgium University College London Director of Urogynecology
The National Hospital for Neurology and The Christ Hospital
Peter Dockery BSc, PhD Neurosurgery Clinical Professor of Obstetrics and
Established Professor of Anatomy London, UK Gynecology
Anatomy School of Medicine University of Cincinnati
National University of Ireland, Galway James J Going MB, ChB, PhD, MRCP, Cincinnati, OH, USA
Galway, Ireland FRCPath
Consultant Pathologist Abraham L Kierszenbaum MD, PhD
Ronald H Douglas BSc, PhD, FLS Queen Elizabeth University Hospital Emeritus Medical (Clinical) Professor of Cell
Professor of Visual Science Glasgow, Scotland Biology and Anatomy
Division of Optometry and Visual Science The City University of New York School of
City, University of London Leonard G Gomella MD, FACS Medicine/Sophie Davis Biomedical
London, UK Professor and Chair Education Program
Department of Urology New York, NY, USA
Klaus D Engel MSc, PhD Thomas Jefferson University
Senior Principal Key Expert Visualization Philadelphia, PA, USA Uday Kishore PhD
Siemens Healthcare GmbH, SHS TE DTI, Brunel University London
Erlangen, Germany Michael A Gorin MD Uxbridge, London, UK
Assistant Professor of Urology
Jaeike Welmoed Faber MD, MSc PhD Johns Hopkins University School of Medicine Aaron J Krych MD
candidate Baltimore, MD, USA Professor
Department of Medical Biology Orthopedic Surgery and Sports Medicine
Amsterdam University Medical Centers Michael A Hall MB ChB, FRCPCH, FRCP, Mayo Clinic
Amsterdam, The Netherlands DCH Rochester, MN, USA
Visiting Professor of Neonatology
Juan C Fernandez-Miranda MD School of Health Sciences Shigeru Kuratani PhD
Associate Professor of Neurological Surgery; University of Southampton Chief Scientist
Associate Director, Center for Cranial Base Southampton, UK Evolutionary Morphology Laboratory
Surgery; RIKEN Cluster for Pioneering Research (CPR)
Director, Surgical Neuroanatomy Laboratory Nobutaka Hirokawa MD, PhD Kobe, Japan
University of Pittsburgh Medical Center Project Professor
Pittsburgh, PA, USA Department of Cell Biology and Anatomy Joey Edward Lai-Cheong BMedSci (Hons),
Graduate School of Medicine, University of MBBS, PhD, FRCP
Erin P Fillmore BA, MPH, PhD Tokyo Consultant Dermatologist
Associate Professor of Clinical Anatomy Tokyo, Japan Frimley Health NHS Foundation Trust
Warwick Medical School, University of Windsor, UK
Warwick Andrea Hofbauer MA
Coventry, UK Global Product Manager Simon Lambert BSc, MBBS, FRCS,
Siemens Healthcare GmbH FRCSEdOrth
Roland A Fleck FRCPath, FRMS Erlangen, Germany Consultant Orthopaedic Surgeon
Professor of Ultrastructural Imaging Department of Trauma and Orthopaedics
Centre for Ultrastructural Imaging University College London Hospital NHS
King’s College London Foundation Trust
London, UK Honorary Consultant Orthopaedic Surgeon
Great Ormond Street Hospital for Children
London, UK
xiii
 CONTRIBUTORS

Robert F LaPrade MD, PhD Antoon FM Moorman PhD Alistair Ross MB, FRCS
Complex Knee Surgeon Emeritus Professor of Embryology Consultant Orthopaedic Surgeon
Twin Cities Orthopedics Department of Medical Biology The Bath Clinic
Edina, MN, USA Amsterdam University Medical Centers Bath, UK
Amsterdam, The Netherlands
John Gerard Lawrenson BSc, MSc (Oxon), Martin Scaal PhD
PhD, FCOptom Gillian Morriss-Kay DSc, Hon FAS Professor of Anatomy and Developmental Biology
Professor of Clinical Visual Science Emeritus Professor of Developmental Anatomy University of Cologne
Division of Optometry and Visual Science Department of Physiology, Anatomy and Cologne, Germany
City, University of London Genetics
London, UK Emeritus Fellow of Balliol College Jeremy D Schmahmann MD, FAAN, FANA,
University of Oxford FANPA
Roger Lemon BSc, PhD, MA, FMedSci Oxford, UK Professor of Neurology
Sobell Professor of Neurophysiology Harvard Medical School;
Queen Square Institute of Neurology Thomas P Naidich MD, FACR Founding Director, Massachusetts General
University College London Professor of Radiology, Neurosurgery & Hospital Ataxia Center
London, UK Pediatrics Director, Laboratory for Neuroanatomy and
Irving and Dorothy Regenstreif Research Cerebellar Neurobiology
James Logan MBBS, BSc, PGDip (SEM), Professor of Neuroscience (Neuroimaging) Cognitive Behavioral Neurology Unit
FRCS (Tr and Orth) Department of Radiology Senior Clinical Neurologist
Orthopaedic Hand Surgeon Icahn School of Medicine at Mt Sinai Department of Neurology
Royal Surrey County Hospital New York, NY, USA Massachusetts General Hospital
Guildford, UK Boston, MA, USA
Donald Anthony Neumann PT, PhD, FAPTA
Marios Loukas MD, PhD Professor, Physical Therapy Program Justine Schober MD
Professor of Anatomy, Dean of Basic Marquette University Director of Academic Research
Sciences Milwaukee, WI, USA Department of Medical Education
Department of Anatomical Sciences Pediatric Urologist
St George’s University Shigeo Okabe MD, PhD Department of Urology
Grenada, West Indies; Department of Cellular Neurobiology UPMC Hamot
Department of Anatomy The University of Tokyo Erie, PA, USA
University of Warmia and Mazury Tokyo, Japan
Olsztyn, Poland Andrew J Sidebottom BDS, FDSRCS (Eng),
Dylan M Owen MSci, MRes, PhD MBChB, FRCS (Eng), FRCS (OMFS)
Ellen A Lumpkin PhD Department of Physics; Consultant Oral and Maxillofacial Surgeon
Professor of Cell & Developmental Biology Randall Division of Cell and Molecular Nottingham University Hospitals
and of Neurobiology Biophysics Honorary Assistant (Consultant) Professor
Department of Molecular & Cell Biology King’s College London University of Nottingham
Helen Wills Neuroscience Institute London, UK Nottingham, UK
University of California, Berkeley
Berkeley, CA, USA Eric M Pauli MD, FACS, FASGE Jonathan MW Slack FMedSci
Professor of Surgery Emeritus Professor of Developmental Biology
Andrew Macdonald BSc (Hons), MB BS, Director of Endoscopic Surgery Department of Biology and Biochemistry
MPhil, FRCSEd (Gen) Chief, Division of Minimally Invasive and University of Bath
Consultant Upper Gastrointestinal Surgeon Bariatric Surgery Bath, UK
Glasgow Royal Infirmary Department of Surgery
Glasgow, UK Penn State Hershey Medical Center Guirish Solanki MBBS, FRCSI, FRCS (SN)
Hershey, PA, USA Consultant Neurosurgeon
M Makarova MD BMI The Priory & Edgbaston Hospital
Institute of Microbiology and Infection Erlick AC Pereira MA, BM, BCh, DM, Birmingham, UK
University of Birmingham FRCS (Neuro Surg), SFHEA
Birmingham, UK Senior Lecturer in Neurosurgery, Honorary Jane C Sowden PhD
Consultant Neurosurgeon Professor of Developmental Biology and Genetics
John A McGrath MD, FRCP, FMedSci St George’s University of London National Institute of Health Research (NIHR)
Mary Dunhill Chair in Cutaneous Medicine St George’s University Hospitals Senior Investigator
St John’s Institute of Dermatology London, UK Head of Stem Cells and Regenerative
King’s College London Medicine Section
London, UK Jeffrey L Ponsky MD UCL Great Ormond Street Institute of Child
Professor of Surgery Health
Seyed Ali Mirjalili MD, PhD, PGDipSurg Department of General Surgery University College London
Senior Lecturer of Anatomy Cleveland Clinic Lerner College of Medicine; London, UK
Anatomy and Medical Imaging Department Professor of Surgery
University of Auckland School of Medicine Robert J Spinner PhD
Auckland, New Zealand Case Western Reserve University Chair, Department of Neurologic Surgery
Cleveland, OH, USA Burton M Onofrio MD Professor of
Zoltán Molnár MD, DPhil Neurosurgery
Professor of Developmental Neurobiology Eitan Prisman MD, MA, FRCSC Professor of Orthopedics and Anatomy
Department of Physiology, Anatomy and Otolaryngology Head and Neck Surgery Mayo Clinic
Genetics and St John’s College University of British Columbia Rochester, MN, USA
University of Oxford Vancouver, BC, Canada
Oxford, UK Jonathan D Spratt MA(Cantab), FRCS(Eng),
Ruth Richardson MA, DPhil, FRHistS FRCR
Garrett D Moore MFA, DPM Senior Visiting Research Fellow Clinical Director of Diagnostic Radiology
Instructor Centre for Life-Writing Research City Hospitals Sunderland NHS Foundation
Department of Orthopedics King’s College London; Trust
University of Colorado, Anschutz Medical Affiliated Scholar in the History and Sunderland, UK;
Campus Philosophy of Science, University of Visiting Professor of Anatomy
Aurora, CO, USA Cambridge, UK Former Anatomy Examiner for the Royal
College of Surgeons of England and Royal
Charles B Rosen MD College of Radiologists
Professor of Surgery
Division of Transplantation Surgery
Mayo Clinic
xiv Rochester, MN, USA
 CONTRIBUTORS

Susan Standring MBE, PhD, DSc, FRBS, Richard Tunstall BMedSci, PhD, FHEA John C Watkinson MSC, MS, FRCS,
FKC, Hon FAS, Hon FRCS Professor of Clinical Anatomy and Imaging FRCS(ENT), DLO
Emeritus Professor of Anatomy Warwick Medical School Honorary Senior Lecturer and Consultant ENT
King’s College London University of Warwick, UK; Queen Elizabeth Hospital, University of
London, UK Professor of Clinical Anatomy Birmingham NHS Trust
West Midlands Surgical Training Centre Royal Marsden and Brompton Hospitals
Mark D Stringer MS, FRCP, FRCS, FRCSEd, UHCW NHS Trust Honorary Consultant Head and Neck and
FRACS Coventry, UK; Thyroid Surgeon
Honorary Professor, Applied Surgical Anatomy Lead University Hospital, Coventry, Warwick NHS
University of Otago Wellington Royal College of Surgeons Trust
Paediatric Surgeon London, UK Honorary Consultant ENT/Head and Neck
Wellington Children’s Hospital and Thyroid Surgeon
Wellington, New Zealand Tom Turmezei MPhil, MA, BMBCh, PhD, FRCR Great Ormond Street Hospital
Consultant Radiologist Honorary Senior Anatomy Demonstrator
Julia Sun MB BCh BAO, BSc, FRCR Norfolk and Norwich University Hospital University College London
Clinical Fellow in Cardiothoracic Radiology Norwich, UK Business Director, Endocrine MDT
Royal Papworth Hospital Honorary Senior Lecturer, University of East The BUPA Cromwell Hospital
Cambridge, UK Anglia, UK London, UK
Royal College of Radiologists 2020 Roentgen
Andrew T Strong MD Professor Adam C Watts MBBS, BSc, FRCS Ed
Clinical Instructor in Surgery (Tr and Ortho)
Department of General Surgery Albert van Schoor BSc MedSci, BSc (Hons) Consultant Elbow Surgeon
Cleveland Clinic Lerner College of Medicine Neuroanatomy, MSc, PhD Upper Limb Unit
of Case Western Reserve University Professor Wrightington Hospital
Cleveland, OH, USA Department of Anatomy Wigan, UK
University of Pretoria
Yosuke Takei MD, PhD Pretoria, South Africa Jonathan Weir-McCall MBChB, PhD, FRCR
Professor University Lecturer and Consultant in
Department of Anatomy and Neuroscience Francesco Vergani MD, PhD, FRCS (Surg Cardiothoracic Radiology in the Royal
Faculty of Medicine Neurol) Papworth Hospital and University of
University of Tsukuba Consultant Neurosurgeon Cambridge
Tsukuba, Japan King’s College Hospital Cambridge, UK
London, UK
Cheryll Tickle CBE, FRS, FRSE, FMedSci, Caroline B Wigley BSc, PhD
HonFRSB, HonFAS Andry Vleeming PhD Retired Preclinical Tutor
Emeritus Professor Professor of Clinical Anatomy University of Exeter Medical School
University of Bath University of New England Exeter, UK
Bath, UK College of Osteopathic Medicine
Biddeford, ME, USA; Jan Wilke
Andoni P Toms MBBS, PhD, FRCR Department of Rehabilitation Sciences and Department of Sports Medicine
Honorary Professor of Radiology Physiotherapy Goethe-Universität Frankfurt am Main
Department of Radiology Faculty of Medicine and Health Sciences Germany
Norfolk & Norwich University Hospital Ghent University
Norwich, UK Ghent, Belgium Frank H Willard PhD
Professor of Anatomy
Kimberly S Topp PT, PhD, FAAA, Hon FAS Dara Walsh BSc University of New England College of
Professor and Chair Emeritus Biomedical Communicator Osteopathic Medicine
Physical Therapy and Rehabilitation Science Graduate Entry Medical School Biddeford, ME, USA
University of California San Francisco University Hospitals Limerick Group
San Francisco, CA, USA University of Limerick Stephanie J Woodley PhD, MSc, BPhty
Limerick, Ireland Associate Professor
R Shane Tubbs MS, PA-C, PhD Department of Anatomy, School of
Professor Jeremy PT Ward PhD, FTPS Biomedical Sciences
Departments of Neurosurgery, Neurology and Emeritus Professor of Respiratory Cell University of Otago
Structural and Cellular Biology Physiology Dunedin, New Zealand
Program Director of Anatomical Research King’s College London
Clinical Neuroscience Research Center London, UK Patrick J Woodman DO, MS, FACOOG
Director of Surgical Anatomy (Dist.), FACS
Tulane University School of Medicine Peter J Ward PhD Clinical Professor of Osteopathic Surgical
New Orleans, LA, USA; Professor of Anatomy Specialties
Professor of Human Gross and Department of Biomedical Sciences Department of Obstetrics & Gynecology
Developmental Anatomy West Virginia School of Osteopathic Urogynecology Division
Department of Anatomical Sciences Medicine Michigan State University College of
St George’s University Lewisburg, WV, USA Osteopathic Medicine
Grenada, West Indies; East Lansing, MI, USA
Faculty David Warwick MD, BM, Dip IMC, Eur Dip
National Skull Base Foundation Hand Surg, FRCS FRCS (Orth) Hoi Tik Hyde Yuen MD
Thousand Oaks, CA, USA; Consultant Hand Surgeon and Honorary Fellow
Professor Professor, Faculty of Medicine Female Pelvic Medicine and Reconstructive
Institute for Systems Biology University Hospital Southampton, Surgery
Seattle WA, USA Southampton, UK The Christ Hospital
Faculty Cincinnati, OH, USA
Department of Neurosurgery and Ochsner Koichi Watanabe MD, PhD
Neuroscience Institute, Ochsner Health Professor of Anatomy Karl Zilles MD, PhD, ML†
System Department of Anatomy Professor of Neuroanatomy
New Orleans, LA, USA Kurume University School of Medicine Institute of Neuroscience and Medicine
Kurume, Japan Research Center Jülich
Abigail Saffron Tucker DPhil, MA, BA Jülich, Germany
Professor of Development & Evolution
Centre for Craniofacial and Regenerative Biology
King’s College London
London, UK
xv
HISTORICAL INTRODUCTION

Gray’s Anatomy is now more than 160 years old. The book is a rarity in with Gray’s publisher, JW Parker & Son, before decisions were taken
textbook publishing in having been in continuous publication on both about the size and girth of the new book, and especially the size of its
sides of the Atlantic Ocean since 1858, an exceptionally long era for a illustrations. While Gray and Carter were working on the book, a new
textbook. Of course, the volume now is very different from the one Mr edition of Quain’s was published; this time it was a ‘triple-decker’ – in
Henry Gray first created with his colleague Dr Henry Vandyke Carter in three volumes – of 1740 pages in all.
mid-Victorian London. In this introductory essay, I shall explain the The two men were earnestly engaged for the following 18 months
long history of Gray’s, from those Victorian days right up to today. in work for the new book. Gray wrote the text, and Carter created the
The shortcomings of existing anatomical textbooks probably illustrations; all the dissections were undertaken jointly. Their working
impressed themselves on Henry Gray when he was still a student at St days were long – all the hours of daylight, eight or nine hours at a
George’s Hospital Medical School, near London’s Hyde Park Corner, in stretch – right through 1856, and well into 1857. We can infer from the
the early 1840s. He began thinking about creating a new anatomy
textbook a decade later, while war was being fought in the Crimea. New
legislation was being planned that would establish the General Medical
Council (1858) to regulate professional education and standards.
Gray was 28 years old, and a teacher himself at St George’s. He was
very able, hard-working and highly ambitious, already a Fellow of the
Royal Society and of the Royal College of Surgeons. Although little is
known about his personal life, his was a glittering career so far, achieved
while he served and taught on the hospital wards and in the dissecting
room (Fig. 1) (Anon 1908).
Gray shared the idea for the new book with a talented clinical col-
league on the teaching staff at St George’s, Henry Vandyke Carter, in
November 1855. Carter was from a family of Scarborough artists, and
was himself a talented artist and experienced microscopist (Fig. 2). He
had produced fine illustrations for Gray’s scientific publications before,
but could see that this idea was a much more complex project. Carter
recorded in his diary:

‘Little to record. Gray made proposal to assist by drawings in bringing

out a Manual for students: a good idea but did not come to any plan
… too exacting, for would not be a simple artist’ (Carter 1855).
Fig. 1 Henry Gray (1827–1861) is shown here in the foreground, seated by
Neither of these young men was interested in producing a pretty the feet of the cadaver. The photograph was taken by a medical student,
book, or an expensive one. Their purpose was to supply an affordable, Joseph Langhorn. The room is the dissecting room of St George’s Hospital
accurate teaching aid for people like their own students, who might Medical School in Kinnerton Street, London. Gray is shown surrounded by
soon be required to operate on real patients, or on soldiers injured at staff and students. When the photo was taken, on 27 March 1860, Carter
Sebastopol or some other battlefield. The book they planned together had left St George’s, to become Professor of Anatomy and Physiology at
was a practical one, designed to encourage youngsters to study anatomy, Grant Medical College, in Bombay (nowadays Mumbai). The second edition
help them pass exams and assist them as budding surgeons. It was not of Gray’s Anatomy was in its proof stages, to appear in December 1860.
simply an anatomy textbook, but a guide to dissecting procedure, and Gray died just over a year later, in June 1861, at the height of his powers.
to the major operations.
Gray and Carter belonged to a generation of anatomists ready to
infuse the study of human anatomy with a new, and respectable, scien-
tificity. Disreputable aspects of the profession’s history, acquired during
the days of body-snatching, were assiduously being forgotten. The
Anatomy Act of 1832 had legalized the requisition of unclaimed bodies
from workhouse and hospital mortuaries, and the study of anatomy
(now with its own Inspectorate) was rising in respectability in Britain.
The private anatomy schools that had flourished in the Regency period
were closing their doors, and the major teaching hospitals were erecting
new, purpose-built dissection rooms (Richardson 2000).
The best-known student works when Gray and Carter had qualified
were probably Erasmus Wilson’s Anatomist’s Vade Mecum, and Elements
of Anatomy by Jones Quain. Both works were small – pocket-sized – but
Quain came in two thick volumes. Their small pages of dense type, and
even smaller illustrations, were somewhat daunting, seeming to demand
much nose-to-the-grindstone effort from the reader.
The planned new textbook’s dimensions and character were serious
matters. Pocket manuals were commercially successful because they
appealed to students by offering much knowledge in a small compass.
But pocket-sized books had button-sized illustrations. Knox’s Manual
of Human Anatomy, for example, was only 6 inches by 4 (15 × 10 cm) Fig. 2 Henry Vandyke Carter (1831–1897). Carter was appointed Honorary
and few of its illustrations occupied more than one-third of a page. Gray Physician to Queen Victoria in 1890. (Self portrait painted while Carter
and Carter must have discussed this matter between themselves, and was in India, courtesy of Professor Susan Standring.) xv.e1
 Historical introduction

warmth of Gray’s appreciation of Carter in his published acknowledge- have allowed him to purchase the long-wished-for microscope he took
ments that their collaboration was a happy one. with him to India.
The first edition print-run of 2000 copies sold out swiftly. A parallel
‘The Author gratefully acknowledges the great services he has derived edition was published in the United States in 1859, and Gray must have
in the execution of this work, from the assistance of his friend, Dr. H. been deeply gratified to have to revise an enlarged new English edition
V. Carter, late Demonstrator of Anatomy at St George’s Hospital. All in 1859–60, though he was surely saddened and worried by the death
the drawings from which the engravings were made, were executed by of his publisher, John Parker junior, at the young age of 40, while the
him, (Gray 1858). book was going through the press. The second edition came out in the
December of 1860 and it too sold like hot cakes.
With all the dissections completed, and Carter’s inscribed wood- The following summer, in June 1861, at the height of his powers and
blocks at the engravers, Gray took six months’ leave from his teaching full of promise, Henry Gray died unexpectedly at the age of only 34.
at St George’s to work as a personal doctor for a wealthy family. It was Gray had contracted smallpox while nursing his nephew. A new strain
probably as good a way as any to get a well-earned break from the dis- of the disease was more virulent than the one with which Gray had
secting room and the dead-house (Nicol 2002). been vaccinated as a child; the disease became confluent, and Gray died
Carter sat the examination for medical officers in the East India in a matter of days.
Company, and sailed for India in the spring of 1858, when the book Within months, the whole country would be pitched into mourning
was still in its proof stages. Gray had left a trusted colleague, Timothy for the death of Prince Albert. The creative era over which he had pre-
Holmes, to see it through the press. Holmes’s association with the first sided – especially the decade that had flowered since the Great Exhibition
edition would later prove vital to its survival. Gray looked over the final of 1851 – would be history.
galley proofs, just before the book finally went to press.

THE BOOK SURVIVES

THE FIRST EDITION
Anatomy Descriptive and Surgical could have died too. With Carter in
The book Gray and Carter had created together, Anatomy, Descriptive and India, the death of Gray, so swiftly after that of the younger Parker,
Surgical, appeared at the very end of August 1858, to immediate acclaim. might have spelled catastrophe. Certainly, at St George’s there was a
Reviews in The Lancet and the British Medical Journal were highly com- sense of calamity. The grand old medical man Sir Benjamin Brodie,
plimentary, and students flocked to buy. Sergeant-Surgeon to the Queen, and to whom Anatomy had been dedi-
It is not difficult to understand why it was a runaway success. Gray’s cated, was a great supporter of Gray and cried forlornly: ‘Who is there
Anatomy knocked its competitors into a cocked hat. It was considerably to take his place?’ (Anon 1908).
smaller and more slender than the doorstopper with which modern But old JW Parker ensured the survival of Gray’s by inviting Timothy
readers are familiar. The book held well in the hand, it felt substantial, Holmes, the doctor who had helped proof-read the first edition, and
and it contained everything required. To contemporaries, it was small who had filled Gray’s shoes at the medical school, to serve as Editor for
enough to be portable, but large enough for decent illustrations: ‘royal the next edition. Other long-running anatomy works, such as that of
octavo’ – 9½ × 6 inches (24 × 15 cm) – about two-thirds of modern A4 Quain, remained in print in a similar way, co-edited by other hands
size. Its medium-size, single-volume format was far removed from (Quain 1856).
Quain’s, yet double the size of Knox’s Manual. Holmes (1825–1907) was another gifted St George’s man, a scholar-
Simply organized and well designed, the book explains itself confi- ship boy who had won an exhibition to Cambridge, where his brilliance
dently and well; the clarity and authority of the prose are manifest. But was recognized. He was a Fellow of the Royal College of Surgeons at
what made it unique for its day was the outstanding size and quality 28. John Parker junior had commissioned him to edit A System of
of the illustrations. Gray thanked the wood engravers Butterworth and Surgery (1860–64), an important essay series by distinguished surgeons
Heath for the ‘great care and fidelity’ they had displayed in the engrav- on subjects of their own choosing. Many of Holmes’s authors remain
ings, but it was really to Carter that the book owed its extraordinary important figures, even today: John Simon, James Paget, Henry Gray,
success. Ernest Hart, Jonathan Hutchinson, Charles-Édouard Brown-Séquard
The beauty of Carter’s illustrations resides in their diagrammatic and Joseph Lister. Holmes had lost an eye in an operative accident, and
clarity, quite atypical for their time. The images in contemporary he had a gruff manner that terrified students, yet he published a lament
anatomy books were usually ‘proxy-labelled’: dotted with tiny numbers for young Parker that reveals him capable of deep feeling (Holmes
or letters (often hard to find or read) or bristling with a sheaf of num- 1860).
bered arrows, referring to a key situated elsewhere, usually in a footnote, John Parker senior’s heart, however, was no longer in publishing.
which was sometimes so lengthy it wrapped round on to the following His son’s death had closed down the future for him. The business, with
page. Proxy labels require the reader’s eye to move to and fro: from the all its stocks and copyrights, was sold to Messrs Longman and Parker
structure to the proxy label to the legend and back again. There was retired to the village of Farnham, where he later died.
plenty of scope for slippage, annoyance and distraction. Carter’s illustra- With Holmes as editor, and Longman as publisher, the immediate
tions, by contrast, unify name and structure, enabling the eye to assimi- future of Gray’s Anatomy was assured. The third edition appeared in
late both at a glance. We are so familiar with Carter’s images that it is 1864 with relatively few changes, Gray’s estate receiving the balance of
hard to appreciate how incredibly modern they must have seemed in his royalty after Holmes was paid £100 for his work.
1858. The volume made human anatomy look new, exciting and
accessible.
The first edition was covered in a brown bookbinder’s cloth embossed THE MISSING OBITUARY
all over in a dotted pattern, and with a double picture-frame border. Its
spine was lettered in gold blocking: Why no obituary appeared for Henry Gray in Gray’s Anatomy is curious.
Gray had referred to Holmes as his ‘friend’ in the preface to the first
GRAY’S edition, yet it would also be true to say that they were rivals. Both had
ANATOMY just applied for a vacant post at St George’s, as Assistant Surgeon. Had
Gray lived, it is thought that Holmes may not have been appointed,
with ‘DESCRIPTIVE AND SURGICAL’ in small capitals underneath. despite his seniority in age (Anon 1908).
Gray’s Anatomy is how it has been referred to ever since. Carter was given Later commentators have suggested, as though from inside knowl-
credit with Gray on the book’s title page for undertaking all the dissec- edge, that Holmes’s ‘proof-reading’ included improving Gray’s writing
tions on which the book was based, and sole credit for all the illustra- style. This could be a reflection of Holmes’s own self-regard, but there
tions, though his name appeared in a significantly smaller type, and he may be some truth in it. There can be no doubt that, as Editor of seven
was described as the ‘Late Demonstrator in Anatomy at St George’s subsequent editions of Gray’s Anatomy (third to ninth editions, 1864–
Hospital’ rather than being given his full current title, which was 1880), Holmes added new material, and had to correct and compress
Professor of Anatomy and Physiology at Grant Medical College, passages, but it is also possible that, back in 1857, Gray’s original
Bombay. Gray was still only a Lecturer at St George’s and he may have manuscript had been left in a poor state for Holmes to sort out. In other
been aware that his words had been upstaged by the quality of Carter’s works, Gray’s writing style was lucid, but he always seems to have paid
anatomical images. He need not have worried: Gray is the famous name a copyist to transcribe his work prior to submission. The original manu-
on the spine of the book. script of Gray’s Anatomy, sadly, has not survived, so it is impossible to
Gray was paid £150 for every thousand copies sold. Carter never be sure how much of the finished version had actually been written by
xv.e2 received a royalty payment, just a one-off fee at publication, which may Holmes.
 HISTORICAL INTRODUCTION

It may be that Gray’s glittering career, or perhaps the patronage that second-rate half-tones altogether. Most of the next edition’s illustrations
unquestionably advanced it, created jealousies among his colleagues, were either Carter’s, or old supplementary illustrations inspired by his
or that there was something in Gray’s manner that precluded affection, work, or newly commissioned wood engravings or line drawings,
or that created resentments among clever social inferiors like Carter and intended ‘to harmonize with Carter’s original figures’. They successfully
Holmes, especially if they felt their contributions to Gray’s brilliant emulated Carter’s verve. Having fewer pages and lighter paper, the 1905
career were not given adequate credit. Whatever the explanation, no (sixteenth edition) weighed less than its predecessor, at 4 lb 11 oz/2.1 kg.
reference to Gray’s life or death appeared in Gray’s Anatomy itself until Typographically, the new edition was superb.
the twentieth century (Howden et al 1918). Howden took over as sole editor in 1909 (seventeenth edition) and
immediately stamped his personality on Gray’s. He excised ‘Surgical’
from the title, changing it to Anatomy Descriptive and Applied, and
A SUCCESSION OF EDITORS removed Carter’s name altogether. He also instigated the beginnings of
an editorial board of experts for Gray’s, by adding to the title page ‘Notes
Holmes expanded areas of the book that Gray himself had developed on Applied Anatomy’ by AJ Jex-Blake and W Fedde Fedden, both St
in the second edition (1860), notably in ‘general’ anatomy (histology) George’s men. For the first time, the number of illustrations exceeded
and ‘development’ (embryology). In Holmes’s time as Editor, the one thousand. Howden was responsible for the significant innovation
volume grew from 788 pages in 1864 to 960 in 1880 (ninth edition), of a short historical note on Henry Gray himself, nearly 60 years after
with the histological section paginated separately in roman numerals his death, which included a portrait photograph (1918, twentieth
at the front of the book. Extra illustrations were added, mainly from edition).
other published sources.
The connections with Gray and Carter, and with St George’s, were
maintained with the appointment of the next editor, T. Pickering Pick, THE NOMENCLATURE CONTROVERSY
who had been a student at St George’s in Gray’s time. From 1883 (tenth
edition) onwards, Pick kept up with current research, rewrote and inte- Howden’s era, and that of his successor TB Johnston (of Guy’s), was
grated the histology and embryology into the volume, dropped Holmes overshadowed by a cloud of international controversy concerning ana-
from the title page, removed Gray’s preface to the first edition, and tomical terminology. European anatomists were endeavouring to stan-
added bold subheadings, which certainly improved the appearance and dardize anatomical terms, often using Latinate constructions, a move
accessibility of the text. Pick said he had ‘tried to keep before himself the resisted in Britain and the United States. Gray’s became mired in these
fact that the work is intended for students of anatomy rather than for the debates for over 20 years. The attempt to be fair to all sides by using
Scientific Anatomist’ (thirteenth edition, 1893). multiple terms doubtless generated much confusion amongst students,
Pick also introduced colour printing (in 1887, eleventh edition) and until a working compromise was at last arrived at in 1955 (thirty-second
experimented with the addition of illustrations using the new printing edition, 1958).
method of half-tone dots: for colour (which worked) and for new black- Johnston oversaw the second retitling of the book (in 1938, twenty-
and-white illustrations (which did not). Half-tone shades of grey com- seventh edition): it was now, officially, Gray’s Anatomy, finally ending
pared poorly with Carter’s wood engravings, still sharp and clear by the fiction that it had ever been known as anything else. Gray’s suffered
comparison. from paper shortages and printing difficulties in World War II, but suc-
What Henry Vandyke Carter made of these changes is a rich topic cessive editions nevertheless continued to grow in size and weight,
for speculation. He returned to England in 1888, having retired from while illustrations were replaced and added as the text was revised.
the Indian Medical Service full of honours, and in 1890 he was made Between Howden’s first sole effort (1909, seventeenth edition) and
Honorary Physician to Queen Victoria. Carter had continued research- Johnston’s last edition (1958, thirty-second edition), Gray’s expanded
ing throughout his clinical medical career in India, and became one of by over 300 pages – from 1296 to 1604 pages, and almost 300 addi-
India’s foremost bacteriologists/tropical disease specialists before there tional illustrations brought the total to over 1300. Johnston also intro-
was really a name for either discipline. He made some important dis- duced X-ray plates (1938) and, in 1958 (thirty-second edition), electron
coveries, including the fungal cause of mycetoma, which he described micrographs by AS Fitton-Jackson, one of the first occasions on which
and named, and he was a key figure in confirming scientifically in India a woman was credited with a contribution to Gray’s. Johnston felt com-
some major international discoveries, such as Hansen’s discovery of the pelled to mention that she was ‘a blood relative of Henry Gray himself’,
cause of leprosy, Koch’s discovery of the organism causing tuberculosis perhaps by way of mitigation.
and Laveran’s discovery of the organism that causes malaria. Carter
married late in life, and his wife was left with two young children when
he died in Scarborough in 1897, aged 65. Like Gray, he received no AFTER WORLD WAR II
obituary in the book, but unlike Gray, Carter received an obituary in
the British Medical Journal that celebrated not only his achievements in The editions of Gray’s issued in the decades immediately following
India but also ‘those excellent illustrations for Gray’s Anatomy which have World War II give the impression of intellectual stagnation. Steady
… contributed so materially to smooth the thorny path of the student of human expansion continued in an almost formulaic fashion, with the insertion
anatomy’ (BMJ 1897). of additional detail. The central historical importance of innovation in
When Pick was joined on the title page by Robert Howden (a profes- the success of Gray’s seems to have been lost sight of by its publishers
sional anatomist from the University of Durham) in 1901 (fifteenth and editors: Johnston (1930–1958, twenty-fourth to thirty-second edi-
edition), the volume was still easily recognizable as the book Gray and tions), J Whillis (co-editor with Johnston, 1938–1954), DV Davies
Carter had created. Although many of Carter’s illustrations had been (1958–1967, thirty-second to thirty-fourth editions) and F Davies (co-
revised or replaced, many others still remained. Sadly, though, an entire editor with DV Davies 1958–1962, thirty-second to thirty-third edi-
section (embryology) was again separately paginated, because its revi- tions). Gray’s had become so pre-eminent that perhaps complacency
sion had taken longer than anticipated. Gray’s Anatomy had grown, crept in, or editors were too daunted or too busy to confront the
seemingly inexorably, and was now quite thick and heavy: 1244 pages, ‘massive undertaking’ of a root and branch revision (Tansey 1995). The
weighing 5 lb 8 oz/2.5 kg. Both co-editors, and perhaps also its pub- unexpected deaths of three major figures associated with Gray’s in this
lisher, were dissatisfied with it. era, James Whillis, Francis Davies and David Vaughan Davies – each of
whom had been ready to take the editorial reins – may have contributed
to retarding the process. The work became somewhat dull.
KEY EDITION: 1905
Serious decisions were taken well in advance of the next edition, which KEY EDITION: 1973
turned out to be Pick’s last with Howden. Published 50 years after Gray
had first suggested the idea to Carter, the 1905 (sixteenth) edition was DV Davies had recognized the need for modernization, but his unex-
a landmark one. pected death left the work to other hands. Two Professors of Anatomy
The period 1880–1930 was a difficult time for anatomical illustra- at Guy’s, Roger Warwick and Peter Williams, the latter of whom had
tion, because the new techniques of photo-lithography and half-tone been involved as an indexer for Gray’s for several years, regarded it as
were not as yet perfected, and in any case could not provide the bold an honour to fulfil Davies’s intentions.
simplicity of line required for a book like Gray’s, which depended so Their thirty-fifth edition of 1973 was a significant departure from
heavily on clear illustration and clear lettering. Recognizing the inferior- tradition. Over 780 pages (of 1471) were newly written, almost a third
ity of half-tone illustrations by comparison with Carter’s wood-engraved of the illustrations were newly commissioned, and the captions for the
originals, Pick and Howden courageously decided to jettison the illustrations were freshly written throughout. With a complete xv.e3
 Historical introduction

re-typesetting of the text in larger double-column pages, a new index The influence of the Warwick and Williams edition was forceful and
and the innovation of a bibliography, this edition of Gray’s looked and long-lasting, and set a new pattern for the following quarter-century. As
felt quite unlike its 1967 (thirty-fourth edition) predecessor, and much has transpired several times before, wittingly or unwittingly, a new
more like its modern incarnation. editor was being prepared for the future: Professor Susan Standring (of
This 1973 edition departed from earlier volumes in other significant Guy’s and subsequently King’s College London), who created the new
ways. The editors made explicit their intention to try to counter the bibliography for the 1973 edition of Gray’s, went on to serve on the
impetus towards specialization and compartmentalization in twentieth- editorial board, and has served as Editor-in-Chief for the last three edi-
century medicine, by embracing and attempting to reintegrate the com- tions before this one (2005–2016, thirty-ninth, fortieth and forty-first
plexity of the available knowledge. Warwick and Williams openly editions). These editions are important for different reasons.
renounced the pose of omniscience adopted by many textbooks, believ- For the thirty-ninth edition, the entire content of Gray’s was reorga-
ing it important to accept and mention areas of ignorance or uncer- nized, from systematic to regional anatomy. This great sea-change was
tainty. They shared with the reader the difficulty of keeping abreast in not just organizational but historic, because, since its outset, Gray’s had
the sea of research, and accepted with a refreshing humility the impos- prioritized bodily systems, with subsidiary emphasis on how the
sibility of fulfilling their own ambitious programme. systems interweave in the regions of the body. Professor Standring
Warwick and Williams’s 1973 edition had much in common with explained that this regional change of emphasis had long been asked
Gray and Carter’s first edition. It was bold and innovative – respectful for by readers and users of Gray’s, and that new imaging techniques had
of its heritage, while also striking out into new territory. It was visually raised the clinical importance of regional anatomy (Standring 2005).
attractive and visually informative. It embodied a sense of a treasury of The change was facilitated by an enormous collective effort on the part
information laid out for the reader (Williams and Warwick 1973). It of the editorial team and the illustrators. The subsequent and current
was published simultaneously in the United States (the American Gray’s editions, now also containing a substantial online-only component
had developed a distinct character of its own in the interval), and sold including an imaging library, consolidate that momentous change (see
extremely well there (Williams and Warwick 1973). Table 1).

TABLE 1 Gray’s Anatomy Editions

Edition Date Author/Editor(s) Publisher Title
1st 1858 Henry Gray JW Parker & Son Anatomy Descriptive and Surgical
The drawings by Henry Vandyke Carter. The dissections jointly by the author and Dr Carter
2nd 1860 Henry Gray JW Parker & Son
3rd 1864 T Holmes Longman
4th 1866 T Holmes Longman
5th 1869 T Holmes Longman
6th 1872 T Holmes Longman
7th 1875 T Holmes Longman
8th 1877 T Holmes Longman
9th 1880 T Holmes Longman
10th 1883 TP Pick Longman
11th 1887 TP Pick Longman
12th 1890 TP Pick Longman
13th 1893 TP Pick Longman
Gray’s preface removed
14th 1897 TP Pick Longman
15th 1901 TP Pick & R Howden Longman
16th 1905 TP Pick & R Howden Longman
17th 1909 Robert Howden Longman Anatomy Descriptive and Applied
Notes on applied anatomy by AJ Jex-Blake & W Fedde Fedden
18th 1913 Robert Howden & Blake & Fedden Longman
19th 1916 Robert Howden & Blake & Fedden Longman
20th 1918 Robert Howden & Blake & Fedden Longman
First edition to feature a photograph and obituary of Henry Gray
21st 1920 Robert Howden Longman
Notes on applied anatomy by AJ Jex-Blake & John Clay
22nd 1923 Robert Howden Longman
Notes on applied anatomy by John Clay & John D Lickley
23rd 1926 Robert Howden Longman
24th 1930 TB Johnston Longman
25th 1932 TB Johnston Longman
26th 1935 TB Johnston Longman
27th 1938 TB Johnston & J Whillis Longman Gray’s Anatomy
28th 1942 TB Johnston & J Whillis Longman
29th 1946 TB Johnston & J Whillis Longman
30th 1949 TB Johnston & J Whillis Longman
31st 1954 TB Johnston & J Whillis Longman
32nd 1958 TB Johnston & DV Davies & F Davies Longman

xv.e4 Continued
 HISTORICAL INTRODUCTION

TABLE 1 Gray’s Anatomy Editions­­—cont’d

Edition Date Author/Editor(s) Publisher Title
33rd 1962 DV Davies & F Davies Longman
34th 1967 DV Davies & RE Coupland Longman
35th 1973 Peter L Williams & Roger Warwick Longman
With a separate volume: Functional Neuroanatomy of Man – being the neurology section of
Gray’s Anatomy, 35th edition, 1975
36th 1980 Roger Warwick & Peter L Williams Churchill Livingstone
37th 1989 Peter L Williams Churchill Livingstone
38th 1995 Peter L Williams & Editorial Board Churchill Livingstone
39th 2005 Susan Standring & Editorial Board Elsevier The Anatomical Basis of Clinical
Practice
40th 2008 Susan Standring & Editorial Board Elsevier The Anatomical Basis of Clinical
Practice
41st 2016 Susan Standring & Editorial Board Elsevier The Anatomical Basis of Clinical
Practice
42nd 2021 Susan Standring & Editorial Board Elsevier The Anatomical Basis of Clinical
Practice

City Museum and Art Gallery, University of Reading, Wellcome Institute

THE DOCTORS’ BIBLE Library, Westminster City Archives and Windsor Castle; and the follow-
ing individuals: Anne Bayliss, Gordon Bell, David Buchanan, Dee Cook,
Neither Gray nor Carter, the young men who – by their committed hard Arthur Credland, Chris Hamlin, Victoria Killick, Louise King, Keith
work between 1856 and 1858 – created the original Gray’s Anatomy, Nicol, Sarah Potts, Mark Smalley and Nallini Thevakarrunai. Above all,
would have conceived that so many years after their deaths their book my thanks to Brian Hurwitz, who has read and advised on the evolving
would not only be a household name, but also be regarded as a work text.
of such pre-eminent importance that a novelist half a world away would
rank it as cardinal – alongside the Bible and Shakespeare – to a doctor’s
education (Sinclair Lewis 1925, Richardson 2008). From this forty- References
second edition of Gray’s Anatomy, we can look back to appraise the
long-term value of their efforts. We can discern how the book they Anon 1908 Henry Gray. St George’s Hospital Gazette 16:49–54.
created triumphed over its competitors, and has survived pre-eminent. BMJ 1897 Henry Vandyke Carter, M.D.Lond. [Obiturary]. Br Med J 1:1256.
Gray’s is a remarkable publishing phenomenon. Although the volume Carter HV 1855 Diary. Wellcome Western Manuscript 5818; 25 Nov.
now looks quite different to the original, and contains so much more, Gray H 1858 Preface. In: Anatomy: Descriptive and Surgical. London: JW
its kinship with the Gray’s Anatomy of 1858 is easily demonstrable by Parker & Son.
direct descent, every edition updated by Henry Gray’s successor. Works Holmes T (ed.) 1860 I: Preface. In: A System of Surgery. London: JW Parker
are rare indeed that have had such a long history of continuous publica- & Son.
tion on both sides of the Atlantic, and such a useful one. Howden R, Jex-Blake AJ, Fedde Fedden W (eds) 1918 Gray’s Anatomy, 20th
ed. London: Longman.
Ruth Richardson, MA, DPhil, FRHistS Nicol KE 2002 Henry Gray of St George’s Hospital: a Chronology. London:
Senior Visiting Research Fellow, Centre for Life-Writing Research, published by the author.
King’s College London; Quain J 1856 Elements of Anatomy. Edited by Sharpey W, Ellis GV. London:
Affiliated Scholar in the History and Philosophy of Science, Walton & Maberly.
University of Cambridge, UK Richardson R 2000 Death, Dissection and the Destitute. Chicago: Chicago
University Press; pp. 193–249, 287, 357.
Richardson R 2008 The Making of Mr Gray’s Anatomy. Oxford: Oxford
University Press.
ACKNOWLEDGEMENTS Sinclair Lewis H 1925 Martin Arrowsmith. New York: Harcourt Brace; p. 4.
Standring S (ed) 2005 Preface. In: Gray’s Anatomy, 39th ed. London:
For their assistance while I was undertaking the research for this essay, Elsevier.
I should like to thank the Librarians and Archivists and Staff at the Tansey EM 1995 A brief history of Gray’s Anatomy. In: Williams PL (ed),
British Library, Society of Apothecaries, London School of Hygiene and Gray’s Anatomy, 38th ed. London: Churchill Livingstone.
Tropical Medicine, Royal College of Surgeons, Royal Society of Medicine, Williams PL, Warwick R (eds) 1973 Preface. In: Gray’s Anatomy, 35th ed.
St Bride Printing Library, St George’s Hospital Tooting, Scarborough London: Churchill Livingstone.

xv.e5
 ANATOMICAL NOMENCLATURE

Anatomy is the study of the structure of the body. Conventionally, it is and lower limbs together with the toes facing forwards (Fig. 1).
divided into topographical (macroscopic or gross) anatomy (which Descriptions are based on four imaginary planes – median, sagittal,
may be further divided into regional anatomy, surface anatomy, neuro- coronal and horizontal – applied to a body in the anatomical position.
anatomy, endoscopic and imaging anatomy); developmental anatomy The median plane passes longitudinally through the body and divides
(embryogenesis and subsequent organogenesis); and the anatomy of it into right and left halves. The sagittal plane is any vertical plane paral-
microscopic and submicroscopic structure (histology). lel with the median plane; although often employed, ‘parasagittal’ is
Anatomical language is one of the fundamental languages of medi- therefore redundant and should not be used. The coronal (frontal)
cine. The unambiguous description of thousands of structures is impos- plane is orthogonal to the median plane and divides the body into
sible without an extensive and often highly specialized vocabulary. anterior (front) and posterior (back). The horizontal (transverse) plane
Ideally, these terms, which are often derived from Latin or Greek, is orthogonal to both median and sagittal planes. Radiologists refer to
should be used to the exclusion of any other, and eponyms should be transverse planes as (trans)axial; convention dictates that axial anatomy
avoided. In reality, this does not always happen. Many terms are ver- is viewed as though looking from the feet towards the head.
nacularized and, around the world, synonyms and eponyms still Structures nearer the head are superior, cranial or (sometimes)
abound in the literature, in medical undergraduate classrooms and in cephalic (cephalad), whereas structures closer to the feet are inferior;
clinics and operating theatres. The 2nd edition of the Terminologia caudal is most often used in embryology to refer to the hind end of the
Anatomica,1 drawn up by the Federative Committee on Anatomical embryo. Medial and lateral indicate closeness to the median plane,
Terminology (FCAT) and newly published in 2019, continues to serve medial being closer than lateral; in the anatomical position, the little
as our reference source for the terminology for macroscopic anatomy, finger is medial to the thumb, and the great toe is medial to the little
and the text of the 42nd edition of Gray’s Anatomy is almost entirely toe. Specialized terms may also be used to indicate medial and lateral.
TA2-compliant. However, where terminology is at variance with, or, Thus, in the upper limb, ulnar and radial are used to mean medial and
more likely, is not included in, the TA, the alternative term used either lateral, respectively; in the lower limb, tibial and fibular (peroneal) are
is cited in the relevant consensus document or position paper, or enjoys used to mean medial and lateral, respectively. Terms may be based on
widespread clinical usage. Synonyms and eponyms are given in paren- embryological relationships; the border of the upper limb that includes
theses on first usage of a preferred term and not shown thereafter in the the thumb, and the border of the lower limb that includes the great toe
text; an updated list of eponyms and short biographical details of the are the pre-axial borders, whilst the opposite borders are the post-axial
clinicians and anatomists whose names are used in this way is available borders. Various degrees of obliquity are acknowledged using com-
in the e-book for reference purposes (see Preface, p. ix, for further dis- pound terms, e.g. posterolateral.
cussion of the use of eponyms). When referring to structures in the trunk and upper limb, we have
When medical students begin dissection classes they are often sur- freely used the synonyms anterior, ventral, flexor, palmar and volar, and
prised by the range of anatomical variation that they encounter amongst posterior, dorsal and extensor. We recognize that these synonyms are
the cadavers in the laboratory. As they progress to clinical examination not always satisfactory, e.g. the extensor aspect of the leg is anterior with
and study their patients’ X-ray, CT, MRI or ultrasound images, they respect to the knee and ankle joints, and superior in the foot and digits;
encounter further variations that prompt the age-old question, ‘what is the plantar (flexor) aspect of the foot is inferior. Dorsal (dorsum) and
normal, and what is beyond the range of anatomical normality?’ The ventral are terms used particularly by embryologists and neuroanato-
interested reader is directed to Bergman’s Comprehensive Encyclopedia of mists; they therefore feature most often in Sections 2 and 3.
Human Anatomic Variation, which ‘attempts to capture many of the Distal and proximal are used particularly to describe structures in
known variants of the human form’.2 the limbs, taking the datum point as the attachment of the limb to the
trunk (sometimes referred to as the root), such that a proximal struc-
ture is closer to the attachment of the limb than a distal structure.
PLANES, DIRECTIONS AND RELATIONSHIPS However, proximal and distal are also used in describing branching
structures, e.g. bronchi, vessels and nerves. External (outer) and inter-
To avoid ambiguity, all anatomical descriptions assume that the body nal (inner) refer to the distance from the centre of an organ or cavity,
is in the conventional ‘anatomical position’, i.e. standing erect and e.g. the layers of the body wall, or the cortex and medulla of the kidney.
facing forwards, upper limbs by the side with the palms facing forwards, External and internal can also describe rotation that is lateral or
medial, respectively, e.g. at the hip or shoulder joints. Superficial and
deep are used to describe the relationships between adjacent struc-
tures. Ipsilateral refers to the same side (of the body, organ or struc-
1
Terminologia Anatomica 2 (2019) is the joint creation of the Federative Committee on ture), bilateral to both sides, and contralateral to the opposite side.
Anatomical Terminology (FCAT) and the Member Associations of the International
Teeth are described using specific terms that indicate their relation-
Federation of Associations of Anatomists (IFAA).
2
Tubbs RS, Shoja MM, Loukas M 2016 Bergman’s Comprehensive Encyclopedia of ship to their neighbours and to their position within the dental arch;
Human Anatomic Variation. Hoboken, NJ: Wiley–Blackwell. these terms are described on page 646.

xvi
 ANATOMICAL NOMENCLATURE

SUPERIOR ASPECT

Coronal plane

Anterior or ventral

Posterior or dorsal

Median or sagittal plane

Inferior or caudal

Superior or cranial
Transverse or horizontal plane Lateral
Medial

POSTERIOR ASPECT

RIGHT LATERAL ASPECT

Lateral (external) rotation

Medial (internal) rotation

Proximal

Distal

Proximal
LEFT LATERAL ASPECT
ANTERIOR ASPECT Supination
Pronation

Distal

Lateral (external) rotation

Medial (internal) rotation

Eversion
Inversion

INFERIOR ASPECT

Fig. 1 The terminology widely used in descriptive anatomy. Abbreviations shown on arrows: AD, adduction; AB, abduction;
FLEX, flexion (of the thigh at the hip joint); EXT, extension (of the leg at the knee joint).
xvii
 CHAPTER

1 Basic structure and function of cells

Epithelial cells rarely operate independently of each other and com-

CELL STRUCTURE monly form aggregates by adhesion, often assisted by specialized inter-
cellular junctions. They may also communicate with each other, either
General characteristics of cells by generating and detecting molecular signals that diffuse across inter-
cellular spaces, or more rapidly by generating interactions between
The shapes of mammalian cells vary widely depending on their interactions membrane-bound signalling molecules. Cohesive groups of cells con-
with each other, their extracellular environment and internal structures. stitute tissues, and more complex assemblies of tissues form functional
Their surfaces are often highly folded when absorptive or transport func- systems or organs.
tions take place across their boundaries. Cell size is limited by rates of Most cells are between 5 and 50 μm in diameter: e.g. resting lym-
diffusion, either that of material entering or leaving cells, or that of diffusion phocytes are 6 μm across, red blood cells 7.5 μm and columnar epithe-
within them. Movement of macromolecules can be much accelerated and lial cells 20 μm tall and 10 μm wide (all measurements are approximate).
also directed by processes of active transport across the plasma membrane Some cells are much larger than this: e.g. megakaryocytes of the bone
and by transport mechanisms within the cell. According to the location of marrow and osteoclasts of the remodelling bone are more than 200 μm
absorptive or transport functions, apical microvilli (Fig. 1.1) or basolateral in diameter. Neurones and skeletal muscle cells have relatively extended
infoldings create a large surface area for transport or diffusion. shapes, some of the former being over 1 m in length.
Motility is a characteristic of most cells, in the form of move-
ments of cytoplasm or specific organelles from one part of the cell
to another. It also includes: the extension of parts of the cell surface Cellular organization
such as pseudopodia, lamellipodia, filopodia and microvilli; loco-
motion of entire cells, as in the amoeboid migration of tissue Each cell is contained within its limiting plasma membrane, which
macrophages; the beating of flagella or cilia to move the cell (e.g. encloses the cytoplasm. All cells, except mature red blood cells, also
in spermatozoa) or fluids overlying it (e.g. in respiratory epithe- contain a nucleus that is surrounded by a nuclear membrane or enve-
lium); cell division; and muscle contraction. Cell movements are lope (see Fig. 1.1; Fig. 1.2). The nucleus includes: the genome of the
also involved in the uptake of materials from their environment cell contained within the chromosomes; the nucleolus; and other sub-
(endocytosis, phagocytosis) and the passage of large molecular nuclear structures. The cytoplasm contains cytomembranes and several
complexes out of cells (exocytosis, secretion). membrane-bound structures, called organelles, which form separate

Surface projections
(cilia, microvilli)

Surface invagination

Actin filaments
Vesicle Mitochondrion

Cell junctions
Plasma membrane

Desmosome Peroxisomes
Cytosol
Nuclear pore
Intermediate
filaments Nuclear envelope

Smooth endoplasmic Nucleus

reticulum
Nucleolus
Ribosome
Rough endoplasmic
reticulum

Microtubules

Golgi apparatus Centriole pair

Lysosomes

Cell surface folds

4 Fig. 1.1 The main structural components and internal organization of a generalized cell.
 1
Basic structure and function of cells

CHAPTER
C MVV
M APM
AJC
Receptor
Transmembrane protein
pore complex
of proteins
Carbohydrate
residues
External
(extracellular)
surface
M
M

Cy

LPM
Internal
(intracellular)
surface Lipid bilayer
N
appearance
in electron
Intrinsic microscope
membrane
protein Extrinsic Transmembrane
protein
protein Transport Non-polar tail
or diffusion of phospholipid
channel Cytoskeletal
Polar end of element
EN phospholipid

Fig. 1.3 The molecular organization of the plasma membrane, according to

the fluid mosaic model of membrane structure. Intrinsic or integral membrane
proteins include diffusion or transport channel complexes, receptor proteins
and adhesion molecules. These may span the thickness of the membrane
(transmembrane proteins) and can have both extracellular and cytoplasmic
domains. Transmembrane proteins have hydrophobic zones, which cross
Fig. 1.2 The structural organization and some principal organelles of a the phospholipid bilayer and allow the protein to ‘float’ in the plane of the
typical cell. This example is a ciliated columnar epithelial cell from human membrane. Some proteins are restricted in their freedom of movement
nasal mucosa. The central cell, which occupies most of the field of view, is where their cytoplasmic domains are tethered to the cytoskeleton.
closely apposed to its neighbours along their lateral plasma membranes.
Within the apical junctional complex, these membranes form a tightly membrane proteins, which are membrane-bound only through their
sealed zone (tight junction) that isolates underlying tissues from, in this association with other proteins. Carbohydrates in the form of oligosac-
instance, the nasal cavity. Abbreviations: AJC, apical junctional complex; charides and polysaccharides are bound either to proteins (glycopro-
APM, apical plasma membrane; C, cilia; Cy, cytoplasm; EN, euchromatic teins) or to lipids (glycolipids), and project mainly into the extracellular
nucleus; LPM, lateral plasma membrane; M, mitochondria; MV, microvilli; domain (Fig. 1.3).
N, nucleolus. (Courtesy of Dr Bart Wagner, Histopathology Department, Combinations of biochemical, biophysical and biological tech-
Sheffield Teaching Hospitals, UK.)
niques have revealed that lipids are not homogeneously distributed in
membranes, but that some are organized into microdomains in the
bilayer, called ‘detergent-resistant membranes’ or lipid ‘rafts’, rich in
sphingomyelin and cholesterol. The ability of select subsets of proteins
and distinct compartments within the cytoplasm. Cytomembranes to partition into different lipid microdomains has profound effects on
include the rough and smooth endoplasmic reticulum and Golgi appa- their function, e.g. in T-cell receptor and cell–cell signalling. The highly
ratus, as well as vesicles derived from them. Organelles include lyso- organized environment of the domains provides a signalling, trafficking
somes, peroxisomes and mitochondria. The nucleus and mitochondria and membrane fusion environment.
are enclosed by a double-membrane system; lysosomes and peroxi- In the electron microscope, membranes fixed and contrasted by
somes have a single bounding membrane. There are also non membrane- heavy metals such as osmium tetroxide appear in section as two densely
bound structures, called inclusions, which lie free in the cytosolic stained layers separated by an electron-translucent zone – the classic
compartment. They include glycogen aggregates and pigments (e.g. unit membrane. The total thickness of each layer is about 7.5 nm. The
lipofuscin). In addition, ribosomes and several filamentous protein overall thickness of the plasma membrane is typically 15 nm. Freeze–
networks, known collectively as the cytoskeleton, are found in the fracture cleavage planes usually pass along the hydrophobic portion of
cytosol. The cytoskeleton determines general cell shape and supports the bilayer, where the hydrophobic tails of phospholipids meet, and
specialized extensions of the cell surface (microvilli, cilia, flagella). It is split the bilayer into two leaflets. Each cleaved leaflet has a surface and
involved in the assembly of specific structures (e.g. centrioles) and a face. The surface of each leaflet faces either the extracellular surface
controls cargo transport in the cytoplasm. The cytosol contains many (ES) or the intracellular or protoplasmic (cytoplasmic) surface (PS). The
soluble proteins, ions and metabolites. extracellular face (EF) and protoplasmic face (PF) of each leaflet are
artificially produced during membrane splitting. This technique has
Plasma membrane also demonstrated intramembranous particles embedded in the lipid
bilayer; in most cases, these represent large transmembrane protein
Cells are enclosed by a distinct plasma membrane, which shares fea- molecules or complexes of proteins. Intramembranous particles are
tures with the cytomembrane system that compartmentalizes the cyto- distributed asymmetrically between the two half-layers, usually adher-
plasm and surrounds the nucleus. All membranes are composed of ing more to one half of the bilayer than to the other. In plasma mem-
lipids (mainly phospholipids, cholesterol and glycolipids) and pro- branes, the intracellular leaflet carries most particles, seen on its face
teins, in approximately equal ratios. Plasma membrane lipids form a (the PF). Where they have been identified, clusters of particles usually
lipid bilayer, a layer two molecules thick. The hydrophobic ends of each represent channels for the transmembrane passage of ions or molecules
lipid molecule face the interior of the membrane and the hydrophilic between adjacent cells (gap junctions).
ends face outwards. Most proteins are embedded within, or float in, the Biophysical measurements show the lipid bilayer to be highly fluid,
lipid bilayer as a fluid mosaic. Some proteins, because of extensive allowing diffusion in the plane of the membrane. Thus proteins are able
hydrophobic regions of their polypeptide chains, span the entire width to move freely in such planes unless anchored from within the cell.
of the membrane (transmembrane proteins), whereas others are only Membranes in general, and the plasma membrane in particular, form
superficially attached to the bilayer by lipid groups. Both are integral boundaries selectively limiting diffusion and creating physiologically
(intrinsic) membrane proteins, as distinct from peripheral (extrinsic) distinct compartments. 5
1
SECTION CELLS, TISSUES AND SYSTEMS

Transport across cell membranes plays a significant role in organ transplant compatibility. The glycocalyx
Most biological molecules cannot diffuse through the phospholipid found on the apical microvilli of enterocytes, the cells forming the
bilayer. Specific transport proteins, such as carrier proteins and channel lining epithelium of the intestine, consists of enzymes involved in the
proteins, mediate the selective passage of molecules across the mem- digestive process. Intestinal microvilli are cylindrical projections
brane, thus allowing the cell to control its internal composition. (1–2 μm long and about 0.1 ts}μm in diameter) forming a closely
Molecules (such as oxygen and carbon dioxide) can cross the plasma packed layer called the brush border that increases the absorptive func-
membrane down their concentration gradients by dissolving first in the tion of enterocytes (see Fig. 1.26).
phospholipid bilayer and then in the aqueous environment at the
cytosolic or extracellular side of the membrane. This mechanism, Cytoplasm
known as passive diffusion, does not involve membrane proteins. Lipid
and lipid-soluble (e.g. steroid) substances can also cross the bilayer. Compartments and functional organization
Other biological molecules (such as glucose, charged molecules and The cytoplasm consists of the cytosol and two cytomembrane systems,
small ions H+, Na+, K+ and Cl–) are unable to dissolve in the hydro- the endoplasmic reticulum and Golgi apparatus, all enclosed by the cell
phobic interior of the phospholipid bilayer. They require the help of or plasma membrane. The cytosol is a gel-like material made up of col-
specific transport proteins (Fig. 1.4) and channel proteins, which facili- loidal proteins such as enzymes, carbohydrates and small protein mol-
tate the passage or facilitated diffusion of most biological molecules. ecules, together with ribosomes and ribonucleic acids. The cytoplasm
Facilitated diffusion requires carrier proteins, which can bind specific also contains membrane-bound organelles (lysosomes, peroxisomes
molecules to be transported, or channel proteins, which form open and mitochondria), membrane-free inclusions (glycogen and pigments)
gates through the membrane. Carrier proteins transport sugars, amino and the cytoskeleton. The nuclear contents, the nucleoplasm, are sepa-
acids and nucleosides. Channel proteins are ion channels involved in rated from the cytoplasm by the nuclear envelope.
the rapid transport of ions (faster transport than that mediated by
carrier proteins), are highly selective of molecular size and electrical Endoplasmic reticulum
charge, and are not continuously open. Ligand-gated channels open The endoplasmic reticulum is a system of interconnecting membrane-
‘gates’ in response to the binding of a signalling molecule, whereas lined channels within the cytoplasm (Fig. 1.5). These channels take
voltage-gated channels open in response to changes in electric potential various forms, including cisternae (flattened sacs), tubules and vesicles.
across the membrane. Similar to passive diffusion, facilitated diffusion The membranes divide the cytoplasm into two major compartments.
of biological molecules is determined by concentration and electrical The intramembranous compartment, or cisternal space, is where secre-
gradients across a membrane. tory products are stored or transported to the Golgi complex and cell
There are three types of transport protein: uniporter, symporter, and exterior: it is continuous with the perinuclear space.
antiporter (see Fig. 1.4). Uniporter transport proteins can be either Structurally, the channel system can be divided into rough or granu-
channel proteins or carrier proteins. They are involved in facilitated lar endoplasmic reticulum (RER), which has ribosomes attached to its
diffusion and carry a single molecule at a time from one side of the outer, cytosolic surface, and smooth or agranular endoplasmic reticu-
membrane to the other along its concentration gradient. Symporter and lum (SER), which lacks ribosomes. The functions of the endoplasmic
antiporter transport proteins are involved in active transport, where the reticulum vary greatly and include the synthesis, folding and transport
transporter utilizes energy, in the form of adenosine triphosphate (ATP) of proteins; the biosynthesis and transport of phospholipids and
to mobilize molecules against their concentration gradient in order to
maintain the correct concentrations of ions and molecules in cells.
Symporter transport proteins are co-transporters (such as the glucose–
sodium co-transporter): they carry two molecules simultaneously or
sequentially in the same direction. Antiporter transport proteins, such
as the sodium–potassium pump, carry two molecules simultaneously
or sequentially in the opposite direction to each other.

Translocation of proteins across intracellular membranes

Proteins are generally synthesized on ribosomes in the cytosol or on
the rough endoplasmic reticulum: a few are made on mitochondrial
ribosomes. Once synthesized, many proteins remain in the cytosol,
where they carry out their functions. Others, such as integral membrane
proteins or proteins for secretion, are translocated across intracellular
membranes for post-translational modification and targeting to their
destinations. This is achieved by the signal sequence, an addressing
system contained within the protein sequence of amino acids, which is
recognized by receptors or translocators in the appropriate membrane. A
Proteins are sorted by their signal sequence (or set of sequences that
become spatially grouped as a signal patch when the protein folds into
its tertiary configuration), in order that they are recognized by and enter
the correct intracellular membrane compartment.
Plasma membrane proteins also provide surfaces for the attachment
of enzymes; sites for the receptors of external signals, including hor-
mones and other ligands; and sites for the recognition and attachment
of other cells. Internally, plasma membranes can act as points of attach-
ment for intracellular structures, in particular those concerned with cell
motility and other cytoskeletal functions. Cell membranes are synthe-
R
sized by the rough endoplasmic reticulum in conjunction with the
Golgi apparatus.

Cell coat (glycocalyx)

The external surface of a plasma membrane differs structurally from
internal membranes in that it possesses an external, fuzzy, carbohy-
drate-rich coat, the glycocalyx, composed of the carbohydrate portions
of glycoproteins and glycolipids embedded in the plasma membrane B
(see Fig. 1.3). The cell coat forms an integral part of the plasma mem-
brane, projecting as a diffusely filamentous layer 2–20 nm or more from Fig. 1.5 A, Smooth endoplasmic reticulum with associated vesicles. The
the lipoprotein surface. dense particles are glycogen granules. B, Rough endoplasmic reticulum
The precise composition of the glycocalyx varies with cell type; many (R), where enclosed cisternae of endoplasmic reticulum are studded with
tissue and cell type-specific antigens are located in the coat, including ribosomes on their cytoplasmic surfaces. (A, Courtesy of Rose Watson,
the major histocompatibility complex of the immune system and, in Cancer Research UK. B, Courtesy of Dr Bart Wagner, Histopathology
6 the case of erythrocytes, blood group antigens. The glycocalyx therefore Department, Sheffield Teaching Hospitals, UK.)
 1
Basic structure and function of cells

CHAPTER
Membrane transporters The glycocalyx plays a significant role in maintenance of the integrity
of tissues and in a wide range of dynamic cellular processes, e.g. serving
as a vascular permeability barrier and transducing fluid shear stress to
Uniporter Symporter Antiporter the endothelial cell cytoskeleton (Weinbaum et al 2007). Disruption of
the glycocalyx on the endothelial surface of large blood vessels precedes
inflammation, a conditioning factor of atheromatosis (e.g. deposits of
cholesterol in the vascular wall leading to partial or complete obstruc-
tion of the vascular lumen).

ATP ATP

Passive transport Active transport

Fig. 1.4 Transporter proteins. Uniporter transport proteins are involved
in facilitated diffusion (passive transport without an energy source). They
carry a single molecule at a time from one side of the membrane to the
other along its concentration gradient. Symporter and antiporter trans-
port proteins are involved in active transport. In active transport, unlike
passive transport, the transporter utilizes energy, in the form of adenosine
triphosphate (ATP) to mobilize molecules against their concentration
gradient. Symporter transport proteins are co-transporters (such as the
glucose–sodium co-transporter); they carry two molecules simultaneously
or sequentially in the same direction. Antiporter transport proteins, such
as the sodium–potassium pump, carry two molecules simultaneously or
sequentially in the opposite direction. (With permission from Kierszenbaum
AL, Tres LL Histology and Cell Biology: An Introduction to Pathology, 5th
ed. Elsevier. Copyright 2019.)

6.e1
 1
Basic structure and function of cells

CHAPTER
steroids; the degradation of glycogen; and the maintenance of calcium Protein synthesis on ribosomes may be suppressed by a class of RNA
homeostasis. Endoplasmic reticulum (ER)-associated degradation molecules known as small interfering RNA (siRNA) or silencing RNA.
(ERAD) is part of the cellular protein quality control system and is These molecules are typically 20–25 nucleotides in length and bind (as
responsible for the clearance of misfolded proteins from the ER for a complex with proteins) to specific mRNA molecules via their comple-
cytosolic proteasomal degradation. mentary sequence. This triggers the enzymatic destruction of the mRNA
In general, RER is well developed in cells that produce abundant or prevents the movement of ribosomes along it. Synthesis of the
proteins, whereas SER is abundant in steroid-producing cells and encoded protein is thus prevented. Their normal function may have
muscle cells. The sarcoplasmic reticulum is a variant of the endoplasmic antiviral or other protective effects; there is also potential for developing
reticulum in muscle cells: it is involved in calcium storage and release artificial siRNAs as a therapeutic tool for silencing disease-related genes.
for muscle contraction. For further reading on the endoplasmic reticu-
lum, see Bravo et al (2013). Golgi apparatus (Golgi complex)
The Golgi apparatus is a distinct cytomembrane system located near the
Smooth endoplasmic reticulum nucleus and the centrosome. It is particularly prominent in secretory
The smooth endoplasmic reticulum (Fig. 1.5A) is associated with carbo- cells and can be visualized when stained with silver or other metallic
hydrate metabolism and many other metabolic processes, including salts. Traffic between the endoplasmic reticulum and the Golgi appara-
detoxification and synthesis of lipids, cholesterol and steroids. The mem- tus is bidirectional and takes place via carrier vesicles derived from the
branes of the smooth endoplasmic reticulum serve as surfaces for the donor site that bud, tether and fuse with the target site. Carrier vesicles
attachment of many enzyme systems, e.g. the enzyme cytochrome P450, in transit from the endoplasmic reticulum to the Golgi apparatus
which is involved in important detoxification mechanisms and is thus (anterograde transport) are coated by coat protein complex II (COPII),
accessible to its substrates, which are generally lipophilic. The smooth whereas COPI-containing vesicles function in the retrograde transport
endoplasmic reticulum in hepatocytes (which are able to store glycogen) route from the Golgi apparatus (reviewed in Spang (2013)).
contains the enzyme glucose-6-phosphatase, which converts glucose- Golgins are long coiled-coil proteins attached to the cytoplasmic
6-phosphate to glucose, a step in gluconeogenesis. The membranes also surface of cisternal membranes, forming a fibrillar matrix surrounding
cooperate with the rough endoplasmic reticulum and the Golgi appara- the Golgi apparatus to stabilize it; they have a role in vesicle trafficking
tus to synthesize new membranes; the protein, carbohydrate and lipid (Witkos and Lowe 2015). The Golgi apparatus has several functions:
components are added in different structural compartments. it links anterograde and retrograde protein and lipid flow in the secre-
tory pathway; it is the site where protein and lipid glycosylation occurs;
Rough endoplasmic reticulum and it provides membrane platforms to which signalling and sorting
The rough endoplasmic reticulum is a site of protein synthesis; its proteins bind.
cytosolic surface is studded with ribosomes (Fig. 1.5B). Ribosomes only Ultrastructurally, the Golgi apparatus (Fig. 1.6A) displays a continu-
bind to the endoplasmic reticulum when proteins targeted for secretion ous ribbon-like structure consisting of a stack of several flattened mem-
begin to be synthesized. Most proteins pass through its membranes and branous cisternae, together with clusters of vesicles surrounding its
accumulate within its cisternae, although some integral membrane pro- surfaces. Cisternae differ in their enzymatic content and activity. Small
teins, e.g. plasma membrane receptors, are inserted into the rough transport vesicles from the rough endoplasmic reticulum are received at
endoplasmic reticulum membrane, where they remain. After passage one face of the Golgi stack, the convex cis-face (entry or forming surface).
from the rough endoplasmic reticulum, proteins remain in membrane- Here, they deliver their contents to the first cisterna in the series by
bound cytoplasmic organelles such as lysosomes, become incorporated membrane fusion. The protein is transported from the edges of this
into new plasma membrane, or are secreted by the cell. Some carbohy- cisterna to the next cisterna by vesicular budding and then fusion, and
drates are also synthesized by enzymes within the cavities of the rough this process is repeated across medial cisternae until the final cisterna at
endoplasmic reticulum and may be attached to newly formed protein the concave trans-face (exit or condensing surface) is reached. Here,
(glycosylation). Vesicles are budded off from the rough endoplasmic larger vesicles are formed for delivery to other parts of the cell.
reticulum for transport to the Golgi as part of the protein-targeting The cis-Golgi and trans-Golgi membranous networks form an inte-
mechanism of the cell gral part of the Golgi apparatus (Fig. 1.6B). The cis-Golgi network is a
region of complex membranous channels interposed between the
Ribosomes, polyribosomes and protein synthesis rough endoplasmic reticulum and the Golgi cis-face, which receives and
Ribosomes are macromolecular machines that catalyse the synthesis of transmits vesicles in both directions. Its function is to select appropriate
proteins from amino acids; synthesis and assembly into subunits takes proteins synthesized on the rough endoplasmic reticulum for delivery
place in the nucleolus and includes the association of ribosomal RNA by vesicles to the Golgi stack, while inappropriate proteins are shuttled
(rRNA) with ribosomal proteins translocated from their site of synthesis back to the rough endoplasmic reticulum.
in the cytoplasm. The individual subunits are then transported into the The trans-Golgi network, at the other side of the Golgi stack, is also
cytoplasm, where they remain separate from each other when not a region of interconnected membrane channels engaged in protein
actively synthesizing proteins. Ribosomes are granules approximately sorting. Here, modified proteins processed in the Golgi cisternae are
25 nm in diameter, composed of rRNA molecules and proteins assem- packaged selectively into vesicles and dispatched to different parts of
bled into two unequal subunits. The subunits can be separated by their the cell. The packaging depends on the detection, by the trans-Golgi
sedimentation coefficients (S) in an ultracentrifuge into larger 60S and network, of particular amino acid signal sequences, leading to their
smaller 40S components. These are associated with 73 different pro- enclosure in membranes of appropriate composition that will further
teins (40 in the large subunit and 33 in the small), which have structural modify their contents, e.g. by extracting water to concentrate them
and enzymatic functions. Three small, highly convoluted rRNA strands (vesicles entering the exocytosis pathway) or by pumping in protons to
(28S, 5.8S and 5S) make up the large subunit, and one strand (18S) is acidify their contents (lysosomes destined for the intracellular sorting
in the small subunit. pathway). The membranes contain specific signal proteins that may
A typical cell contains millions of ribosomes. They may form groups allocate them to microtubule-based transport pathways and allow them
(polyribosomes or polysomes) attached to messenger RNA (mRNA), to dock with appropriate targets elsewhere in the cell, e.g. the plasma
which they translate during protein synthesis for use outside the system membrane in the case of secretory vesicles. Vesicle formation and
of membrane compartments, e.g. enzymes of the cytosol and cytoskel- budding at the trans-Golgi network involves the addition of clathrin on
etal proteins. Some of the cytosolic products include proteins that can their external surface, to form coated pits.
be inserted directly into (or through) membranes of selected organelles, Within the Golgi stack proper, proteins undergo a series of sequen-
such as mitochondria and peroxisomes. Ribosomes may be attached to tial chemical modifications by Golgi resident enzymes synthesized in
the membranes of the rough endoplasmic reticulum (see Fig. 1.5B). the rough endoplasmic reticulum. These include glycosylation (changes
In a mature polyribosome, all the attachment sites of the mRNA are in glycosyl groups, e.g. removal of mannose, addition of
occupied as ribosomes move along it, synthesizing protein according N-acetylglucosamine and sialic acid); sulphation (addition of sulphate
to its nucleotide sequence. Consequently, the number and spacing of groups to glycosaminoglycans); and phosphorylation (addition of
ribosomes in a polyribosome indicate the length of the mRNA mole- phosphate groups). Some modifications serve as signals to direct pro-
cule and hence the size of the protein being made. The two subunits teins and lipids to their final destination within cells, including lyso-
have separate roles in protein synthesis. The 40S subunit is the site of somes and plasma membrane. Lipids formed in the endoplasmic
attachment and translation of mRNA. The 60S subunit is responsible reticulum are also routed for incorporation into vesicles.
for the release of the new protein and, where appropriate, attachment
to the endoplasmic reticulum via an intermediate docking protein that Exocytic (secretory) pathway
directs the newly synthesized protein through the membrane into the Secreted proteins, lipids, glycoproteins, small molecules such as amines,
cisternal space. and other cellular products destined for export from the cell are 7
1
SECTION CELLS, TISSUES AND SYSTEMS

transported to the plasma membrane in small vesicles released from correct plasma membrane domains is achieved by sorting sequences in
the trans-face of the Golgi apparatus. This pathway is either constitutive, the cytoplasmic tails of vesicular membrane proteins.
in which transport and secretion occur more or less continuously, as
with immunoglobulins produced by plasma cells, or it is regulated by Endocytic (internalization) pathway
external signals, as in the control of salivary secretion by autonomic The endocytic pathway begins at the plasma membrane and ends in
neural stimulation. In regulated secretion, the secretory product is lysosomes (see below) involved in the degradation of the endocytic
stored temporarily in membrane-bound secretory granules or vesicles. cargo through the enzymatic activity of lysosomal hydrolases. Endocytic
Exocytosis is achieved by fusion of the secretory vesicular membrane cargo is internalized from the plasma membrane to early endosomes
with the plasma membrane and release of the vesicle contents into the and then to late endosomes. Late endosomes transport their cargo to
extracellular domain. In polarized cells, e.g. most epithelia, exocytosis lysosomes, where the cargo material is degraded following fusion and
occurs at the apical plasma membrane. Glandular epithelial cells secrete mixing of contents of endosomes and lysosomes. Early endosomes
into a duct lumen, as in the pancreas, or on to a free surface, such as derive from endocytic vesicles (clathrin-coated vesicles and caveolae).
the lining of the stomach. In hepatocytes, bile is secreted across a very Once internalized, endocytic vesicles shed their coat of adaptin and
small area of plasma membrane forming the wall of the bile canalicu- clathrin, and fuse to form an early endosome, where the receptor mol-
lus. This region, the apical plasma membrane, is the site of exocrine ecules release their bound ligands. Membrane and receptors from the
secretion, whereas secretion of hepatocyte plasma proteins into the early endosomes can be recycled to the cell surface as exocytic
blood stream is targeted to the basolateral surfaces facing the sinusoids. vesicles.
Packaging of different secretory products into appropriate vesicles takes Clathrin-dependent endocytosis occurs at specialized patches of
place in the trans-Golgi network. Delivery of secretory vesicles to their plasma membrane called coated pits: this mechanism is also used to

Vesicles derived from the

trans-Golgi constitute the
trans-Golgi network (TGN). TGN is
the sorting site of cargoes for
secretion or transport to lysosomes

Vesicles shuttling trans-Golgi

between cisternae

Ribbon cisternae of the medial-Golgi

cis-Golgi

Endoplasmic reticulum

Receptor-mediated
endocytosis pathway
B Secretory pathway
LDL

Phagocytic pathway LDL receptor

Lysosome pathway
Phagosome Clathrin-coated pit
Primary
Phagolysosome lysosome Secretory
vesicle Early endosome
Secondary lysosome

Residual body trans-Golgi Clathrin uncoating

Late endosome

Macroautophagy medial-Golgi

Mitochondrion Recycled membrane and

cis-Golgi
Autophagosome LDL receptor

Smooth endoplasmic
Free cholesterol
reticulum

Vesicles shuttling between

Rough endoplasmic reticulum cisternae

Fig. 1.6 A, The Golgi apparatus consists of four major functionally distinct compartments. Products derived from the
endoplasmic reticulum enter the Golgi apparatus at the cis-Golgi. Cargoes exit at the trans-Golgi. The medial-Golgi is a
stack of ribbon-like cisternae interposed between the cis-Golgi and the trans-Golgi. Cargoes destined for transport to
lysosomes or secretion (exocytosis) are sorted in the trans-Golgi network (TGN). B, There are three major pathways for
the intracellular degradation of materials. Extracellular particles can be taken up by phagocytosis and receptor-mediated
endocytosis. Aged intracellular components are degraded by macroautophagy, a non-selective process. The Golgi apparatus
releases vesicles for secretion or lysosome-containing vesicles that remain in the cell. Lysosomes are organelles that
8 contain about 40 types of hydrolytic enzymes active in an acidic environment (pH approximately 5.0).
 1
Basic structure and function of cells

CHAPTER
C D
Primary lysosomes Mitochondrion Secondary lysosomes
(inactive)

Fig. 1.6, cont’d C, Primary lysosomes are inactive storage sites for hydrolytic enzymes. D, Secondary lysosomes are
engaged in degradation and contain remnants of the degraded structures. (A, C and D with permission from Kierszenbaum
AL, Tres LL Histology and Cell Biology: An Introduction to Pathology, 5th ed. Elsevier. Copyright 2019.)

internalize ligands bound to surface receptor molecules and is also inert residual body. Considerable numbers of residual bodies can accu-
termed receptor-mediated endocytosis. Caveolae are structurally dis- mulate in long-lived cells, often fusing to form larger dense vacuoles
tinct pinocytotic vesicles most widely used by endothelial and smooth with complex lamellar inclusions. As their contents are often darkly
muscle cells, where they are involved in transcytosis, signal transduc- pigmented, this may change the colour of the tissue; e.g. in neurones,
tion and possibly other functions. In addition to late endosomes, lyso- the end-product of lysosomal digestion, lipofuscin (neuromelanin or
somes can also fuse with phagosomes, autophagosomes and plasma senility pigment), gives ageing brains a brownish-yellow coloration.
membrane patches for membrane repair. Lysosomal hydrolases process Lysosomal enzymes may also be secreted – often as part of a process
or degrade exogenous materials (phagocytosis or heterophagy) as well to alter the extracellular matrix, as in osteoclast-mediated erosion
as endogenous material (autophagy). Phagocytosis consists of the cel- during bone resorption. For further reading on lysosome biogenesis,
lular uptake of invading pathogens, apoptotic cells and other foreign see Saftig and Klumperman (2009).
material by specialized cells. Lysosomes are numerous in actively
phagocytic cells, e.g. macrophages and neutrophil granulocytes, where Lysosomal dysfunction
they are responsible for destroying phagocytosed particles, e.g. bacteria. The transcription factor EB (TFEB) is responsible for regulating lyso-
These cells may contain phagosomes, vesicles that potentially contain somal biogenesis and function, lysosome-to-nucleus signalling and
a pathogenic microorganism and that may fuse with several lipid catabolism (for further reading, see Settembre et al (2013)). If
lysosomes. there is a failure of any of the actions of lysosomal hydrolases, of the
Specialized cells of the immune system, antigen-presenting cells lysosome acidification mechanism or of lysosomal membrane pro-
(APCs), degrade protein molecules (antigens) transported by the endo- teins, there is progressive lysosomal dysfunction in several tissues and
cytic pathway for lysosomal breakdown, and expose their fragments to organs. This may be due to faulty degradation and recycling of extra-
the cell exterior to elicit an immune response, that is mediated initially cellular substrates delivered to lysosomes by the late endosome or the
by helper T cells. defective degradation and recycling of intracellular substrates by
Late endosomes receive lysosomal enzymes from primary lysosomes autophagy.
(Fig. 1.6C) derived from the Golgi apparatus after late endosome–lyso- Lysosomal storage disorders (LSDs) are a consequence of lysosomal
some membrane tethering and fusion followed by diffusion of lyso- dysfunction. Approximately 60 different types of LSD have been identi-
somal contents into the endosomal lumen. The pH inside the fused fied on the basis of the type of material accumulated in cells (such as
hybrid organelle, now called a secondary lysosome, is low (about 5.0): mucopolysaccharides, sphingolipids, glycoproteins, glycogen and
this activates lysosomal acid hydrolases to degrade the endosomal con- lipofuscins).
tents. The products of hydrolysis are either passed through the mem-
brane into the cytosol, or they may be retained in the secondary Peroxisomes
lysosome (Fig. 1.6D). Secondary lysosomes may grow considerably in Peroxisomes are small (0.2–1 μm in diameter) membrane-bound
size by vesicle fusion to form multivesicular bodies; the enzyme con- organelles present in most mammalian cells. They contain more than
centration may increase greatly to form large lysosomes. 50 enzymes responsible for multiple catabolic and synthetic biochemi-
cal pathways, in particular the β-oxidation of very-long-chain fatty acids
Lysosomes (>C22) and the metabolism of hydrogen peroxide (hence the name
Lysosomes are membrane-bound organelles 80–800 nm in diameter, peroxisome). Peroxisomes may be derived from pre-existing peroxi-
often with complex inclusions of material undergoing hydrolysis (sec- somes that divide by fission. Alternatively, they may arise de novo by
ondary lysosomes). Two classes of protein participate in lysosomal budding as pre-peroxisomal vesicles from the endoplasmic reticulum
function, namely soluble acid hydrolases and integral lysosomal mem- and possibly from mitochondria (Farré et al 2019). All matrix proteins
brane proteins. Each of the 60 or more known acid hydrolases (includ- and some peroxisomal membrane proteins are synthesized by cytosolic
ing proteases, lipases, carbohydrases, esterases and nucleases) degrades ribosomes and contain a peroxisome targeting signal that enables them
a specific substrate. There are about 25 lysosomal membrane proteins to be imported by proteins called peroxins (Braverman et al 2013,
participating in the acidification of the lysosomal lumen, protein Theodoulou et al 2013).
import from the cytosol, membrane fusion and transport of degrada- Peroxisomes often contain crystalline inclusions composed mainly
tion products to the cytoplasm. Material that has been hydrolysed of high concentrations of the enzyme urate oxidase. Oxidases use
within secondary lysosomes may be completely degraded to soluble molecular oxygen to oxidize specific organic substrates (such as l-
products, e.g. amino acids, which are recycled through metabolic path- amino acids, d-amino acids, urate, xanthine and very-long-chain fatty
ways. However, degradation is usually incomplete and some debris acids) and produce hydrogen peroxide that is detoxified (degraded) by
remains. A debris-laden vesicle is called a residual body or tertiary lyso- peroxisomal catalase. Peroxisomes are important in the oxidative detox-
some (see Fig. 1.6B), and may be passed to the cell surface, where it is ification of various substances taken into or produced within cells. They
ejected by exocytosis; alternatively, it may persist inside the cell as an are particularly numerous in hepatocytes. 9
 1
Basic structure and function of cells

CHAPTER
LSDs are characterized by severe neurodegeneration, mental decline, myopathy and cardiomyopathy with neurodegeneration in hemizygous
and cognitive and behavioural abnormalities. Autophagy impairment males, lysosomes fail to fuse with autophagosomes because of a muta-
caused by defective lysosome–autophagosome coupling triggers a patho- tion of the lysosomal membrane protein LAMP-2 (lysosomal-associated
genic cascade by the accumulation of substrates that contribute to neu- membrane protein-2).
rodegenerative disorders, including Parkinson's disease, Alzheimer's Peroxin mutation is a characteristic feature of Zellweger syndrome
disease, Huntington's disease and several tau-opathies. In Tay–Sachs (craniofacial dysmorphism and malformations of brain, liver, eye and
disease (GM2 gangliosidosis), a faulty β-hexosaminidase A leads to the kidney; cerebrohepatorenal syndrome). Neonatal leukodystrophy is an
accumulation of the glycosphingolipid GM2 ganglioside in neurones, X-linked peroxisomal disease affecting mostly males, caused by defi-
causing death during childhood. In Danon disease, a vacuolar skeletal ciency in β-oxidation of very-long-chain fatty acids.

9.e1
1
SECTION CELLS, TISSUES AND SYSTEMS

The build-up of very-long-chain fatty acids in the nervous system whereas those of the cytochrome system and oxidative phosphorylation
and suprarenal glands determines progressive deterioration of brain are localized chiefly in the inner mitochondrial membrane. The inter-
function and suprarenal insufficiency (Addison's disease). For further membrane space houses cytochrome c, a molecule involved in activation
reading, see Braverman et al (2013). of apoptosis.
The number of mitochondria in a particular cell reflects its general
Mitochondria energy requirements; e.g. in hepatocytes there may be as many as 2000,
Mitochondria appear in the light microscope as long, thin structures in whereas in resting lymphocytes there are usually very few. Mature eryth-
the cytoplasm of most cells, particularly those with a high metabolic rocytes lack mitochondria altogether. Cells with few mitochondria gen-
rate, e.g. secretory cells in exocrine glands. In the electron microscope, erally rely largely on glycolysis for their energy supplies. These include
mitochondria usually appear as round or elliptical bodies 0.5–2.0 μm some very active cells, e.g. fast-twitch skeletal muscle fibres, which are
long (Fig. 1.7), consisting of an outer mitochondrial membrane; an able to work rapidly but for only a limited duration. Mitochondria are
inner mitochondrial membrane, separated from the outer membrane by distributed within a cell according to regional energy requirements, e.g.
an intermembrane space; cristae, infoldings of the inner membrane that near the bases of cilia in ciliated epithelia, in the basal domain of the
harbour ATP synthase to generate ATP; and the mitochondrial matrix, a cells of proximal convoluted tubules in the renal cortex (where consid-
space enclosed by the inner membrane and numerous cristae. The per- erable active transport occurs) and around the proximal segment, called
meability of the two mitochondrial membranes differs considerably: the the middle piece, of the flagellum in spermatozoa. In living cells, mito-
outer membrane is freely permeable to many substances because of the chondria constantly change shape and intracellular position; they mul-
presence of large non-specific channels formed by proteins (porins), tiply by growth and fission, and may undergo fusion.
whereas the inner membrane is permeable to only a narrow range of Mitochondria may be involved in tissue-specific metabolic reactions,
molecules. The presence of cardiolipin, a phospholipid, in the inner e.g. various urea-forming enzymes are found in liver cell mitochondria.
membrane may contribute to this relative impermeability. Moreover, a number of genetic diseases of mitochondria affect particu-
Mitochondria are the principal source of chemical energy in most lar tissues exclusively, e.g. mitochondrial myopathies (skeletal muscle)
cells. They are the site of the citric acid (Krebs') cycle and the electron and mitochondrial neuropathies (nervous tissue).
transport (cytochrome) pathway by which complex organic molecules are The mitochondrial matrix is an aqueous environment. It contains a
finally oxidized to carbon dioxide and water. This process provides the variety of enzymes, and strands of mitochondrial DNA with the capac-
energy to drive the production of ATP from adenosine diphosphate ity for transcription and translation of a unique set of mitochondrial
(ADP) and inorganic phosphate (oxidative phosphorylation). The various genes (mitochondrial mRNAs and transfer RNAs, mitochondrial ribo-
enzymes of the citric acid cycle are located in the mitochondrial matrix, somes with rRNAs). The DNA forms a closed loop, about 5 μm across
and several identical copies are present in each mitochondrion. The
ratio between its bases differs from that of nuclear DNA; the RNA
sequences also differ in the precise genetic code used in protein synthe-
A sis. At least 13 respiratory chain enzymes of the matrix and inner
membrane are encoded by the small number of genes along the mito-
chondrial DNA (mtDNA). The great majority of mitochondrial proteins
are encoded by nuclear genes and made in the cytosol, then inserted
through special channels in the mitochondrial membranes to reach
their destinations. Their membrane lipids are synthesized in the endo-
plasmic reticulum.
Mitochondrial ribosomes are smaller and quite distinct from those
of the rest of the cell in that they (and mitochondrial nucleic acids)
resemble those of bacteria. This similarity underpins the theory that
mitochondrial ancestors were oxygen-utilizing bacteria that existed in
a symbiotic relationship with eukaryotic cells unable to metabolize the
oxygen produced by early plants.
It has been shown that mitochondria are of maternal origin because
the mitochondria of spermatozoa are not generally incorporated into
the ovum at fertilization. As mitochondria are formed only from previ-
ously existing ones, it follows that all mitochondria in the body are
descended from those in the cytoplasm of the ovum. Thus mitochon-
dria (and mitochondrial genetic variations and mutations) are passed
only through the female line. For further information on mitochondrial
genetics and disorders, see Chinnery and Hudson (2013).

B Mitochondrial replacement therapies

Available with the Gray’s Anatomy e-book

Outer membrane Cytosolic inclusions

The aqueous cytosol surrounds the membranous organelles described
Inner membrane above. It also contains various non-membranous inclusions, including
free ribosomes, components of the cytoskeleton, and other inclusions,
Cristae (folds)
such as storage granules (e.g. glycogen), pigments (such as lipofuscin
granules, remnants of the lipid oxidative mechanism seen in the supra-
Elementary renal cortex).
particles

Lipid droplets
Lipid droplets are spherical bodies of various sizes found within
many cells, but are especially prominent in the adipocytes (fat cells)
of adipose connective tissue. They do not belong to the Golgi-related
vacuolar system of the cell. Lipid droplets, suspended in the cytosol,
are surrounded by perilipin proteins, which regulate lipid storage
and lipolysis. (See Smith and Ordovás (2012) for further reading on
obesity and perilipins.) In cells specialized for lipid storage, the
vacuoles reach 80 μm or more in diameter. They function as stores
Fig. 1.7 A, Mitochondria in human cardiac muscle. The folded cristae of chemical energy, thermal insulators and mechanical shock
(arrows) project into the matrix from the inner mitochondrial membrane. absorbers in adipocytes. In many cells, they may represent end-
B, The location of the elementary particles that couple oxidation and products of other metabolic pathways, e.g. in steroid-synthesizing
phosphorylation reactions. (A, Courtesy of Dr Bart Wagner, Histopathology cells, where they are a prominent feature of the cytoplasm. They may
10 Department, Sheffield Teaching Hospitals, UK.) also be secreted, as in the alveolar epithelium of the lactating breast.
 1
Basic structure and function of cells

CHAPTER
Cristae are abundant in mitochondria within cardiac muscle cells and maternal and paternal nuclei are assembled as a pronucleus. Because
in steroid-producing cells (in the suprarenal cortex, corpus luteum and it is difficult to distinguish between male and female pronuclei, pro-
Leydig cells). The protein, steroidogenic acute regulatory protein (StAR), nuclear transfer (PNT) involves transplantation of both the maternal
regulates the synthesis of steroids by transporting cholesterol across the and paternal pronuclei, clearly visualized by light microscopy. mtDNA
outer mitochondrial membrane. A mutation in the gene encoding StAR resides within mitochondria, separately from the genes housed in
causes defective suprarenal and gonadal steroidogenesis. each cell nucleus. Since mitochondria are inherited only through the
Mitochondrial replacement therapies have been developed to maternal germline, mutated mitochondria are thus replaced with
resolve mitochondrial disorders of maternal origin, e.g. by transplan- normal mitochondria from enucleated oocytes provided by the unaf-
tating the pronucleus from an egg containing mutant mtDNA from a fected donor. An alternative procedure involves transfer of the nuclear
carrier mother to an enucleated egg from an unaffected donor (Fig. genetic material from the affected female (maternal spindle transfer,
1.8). This procedure can be performed after in vitro fertilization using MST) into an enucleated donor egg with normal mitochondria, prior
sperm from the intended father. Soon after fertilization, the haploid to fertilization.

Discarded egg with

mutant mtDNA

The pronucleus of the

First polar body First and second carrier mother is placed
polar bodies into the donor’s enucleated
fertilized egg containing
Spindle (completion normal mtDNA. The egg
of meiosis II) (zygote) is implanted into
the carrier mother.

Fertilizing sperm from

the intended father

Fertilization in vitro of a Removal of the pronucleus (paternal

carrier mother’s oocyte and maternal nuclei) from the
containing mutant mtDNA fertilized carrier mother’s egg

Fertilizing sperm from

the intended father Discarded
pronucleus
Fertilization in vitro of a Removal of the pronucleus
donor’s oocyte containing (paternal and maternal nuclei)
normal mtDNA from the donor’s egg
Fig. 1.8 Mitochondrial replacement by pronuclear transfer. Mitochondrial DNA (mtDNA) is transmitted by the mother
(maternal inheritance). Both males and females can be affected by mitochondrial diseases, but males do not transmit
the disorder to their offspring. One mitochondrial replacement therapy involves the transplantation of the pronucleus
from an egg containing mutant mtDNA from a carrier mother to an enucleated egg from an unaffected donor. This can
be performed after in vitro fertilization using sperm from the intended father. (With permission from Kierszenbaum AL,
Tres LL Histology and Cell Biology: An Introduction to Pathology, 5th ed. Elsevier. Copyright 2019.)

10.e1
 1
Basic structure and function of cells

CHAPTER
Cell signalling inside the cell unless they first bind to a plasma membrane receptor
protein. Ligands are mainly proteins (usually glycoproteins), poly-
Cellular systems in the body communicate with each other to coordi- peptides or highly charged biogenic amines. They include classic
nate and integrate their functions, through a variety of processes known peptide hormones of the endocrine system; cytokines, which are
collectively as cell signalling, in which a signalling molecule produced mainly of haemopoietic cell origin and involved in inflammatory
by one cell is detected by another, almost always by means of a specific responses and tissue remodelling (e.g. the interferons, interleukins,
receptor protein molecule. The recipient cell transduces the signal, tumour necrosis factor, leukaemia inhibitory factor); and polypeptide
which it most often detects at the plasma membrane, into intracellular growth factors (e.g. the epidermal growth factor superfamily, nerve
chemical messages that change cell behaviour. growth factor, platelet-derived growth factor, the fibroblast growth
The signal may act over a long distance, e.g. endocrine signalling factor family, transforming growth factor beta and the insulin-like
through the release of hormones into the blood stream, or neuronal growth factors). Polypeptide growth factors are multifunctional mol-
synaptic signalling via electrical impulse transmission along axons and ecules with more widespread actions and cellular sources than their
subsequent release of chemical transmitters of the signal at synapses or names suggest. They and their receptors are commonly mutated or
neuromuscular junctions. A specialized variation of endocrine signal- aberrantly expressed in certain cancers. The cancer-causing gene
ling (neurocrine or neuroendocrine signalling) occurs when neurones variant is termed a transforming oncogene and the normal (wild-
or paraneurones (e.g. chromaffin cells of the suprarenal medulla) secrete type) version of the gene is a cellular oncogene or proto-oncogene.
a hormone into interstitial fluid and the blood stream. Alternatively, The activated receptor acts as a transducer to generate intracellular
signalling may occur at short range through a paracrine mechanism, in signals, which are either small diffusible second messengers (e.g.
which cells of one type release molecules into the interstitial fluid of the calcium, cyclic adenosine monophosphate or the plasma membrane
local environment, to be detected by nearby cells of a different type that lipid-soluble diacylglycerol), or larger protein complexes that amplify
express the specific receptor protein. and relay the signal to target control systems.
Neurocrine cell signalling uses chemical messengers found also in Some signals are hydrophobic and able to cross the plasma mem-
the central nervous system, which may act in a paracrine manner via brane freely. Classic examples are the steroid hormones, thyroid hor-
interstitial fluid or reach more distant target tissues via the blood stream. mones, retinoids and vitamin D. Steroids, for instance, enter cells
Cells may generate and respond to the same signal. This is autocrine non-selectively, but elicit a specific response only in those target cells
signalling, a phenomenon that reinforces the coordinated activities of that express specific cytoplasmic or nuclear receptors. Light stimuli also
a group of like cells, which respond together to a high concentration of cross the plasma membranes of photoreceptor cells and interact intra-
a local signalling molecule. The most extreme form of short-distance cellularly, at least in rod cells, with membrane-bound photosensitive
signalling is contact-dependent (juxtacrine) signalling, where one cell receptor proteins. Hydrophobic ligands are transported in the blood
responds to transmembrane proteins of an adjacent cell that bind to stream or interstitial fluids, generally bound to carrier proteins, and they
surface receptors in the responding cell membrane. Contact-dependent often have a longer half-life and longer-lasting effects on their targets
signalling also includes cellular responses to integrins on the cell surface than do water-soluble ligands.
binding to elements of the extracellular matrix. Juxtacrine signalling is A separate group of signalling molecules that are able to cross the
important during development and in immune responses. These differ- plasma membrane freely is typified by the gas, nitric oxide. The principal
ent types of intercellular signalling mechanism are illustrated in Fig. 1.9. target of short-range nitric oxide signalling is smooth muscle, which
relaxes in response. Nitric oxide is released from vascular endothelium
Signalling molecules and their receptors as a result of the action of autonomic nerves that supply the vessel wall,
The majority of signalling molecules (ligands) are hydrophilic and so causing local relaxation of smooth muscle and consequent dilation of
cannot cross the plasma membrane of a recipient cell to effect changes the vessel. This mechanism is responsible for penile erection. Nitric oxide

A Endocrine B Paracrine
Short-range signalling
molecule
Endocrine cell A
Receptor Y Signalling
Endocrine cell B cell

Receptor X
Target
cells
Target cell B

Different Target cell A

Blood stream hormones

C Autocrine D Synaptic
Neurone
Synapse

Membrane receptor Axon

Hormone or Cell body Neurotransmitter Target cell

growth factor

E Neurocrine F Contact-dependent
Neuroendocrine Neuropeptide
cell or amine
Stimulus Signalling cell Target cell

Blood vessel
Membrane-bound
Distant target cell signal molecule

Fig. 1.9 The different modes of cell–cell signalling. 11

1
SECTION CELLS, TISSUES AND SYSTEMS

is unusual among signalling molecules in having no specific receptor In addition, the cytoskeleton provides tracks for intracellular transport
protein; it acts directly on intracellular enzymes of the response pathway. (e.g. shuttling vesicles and macromolecules, called cargoes, among cyto-
plasmic sites), the movement of chromosomes during cell division
Receptor proteins (mitosis and meiosis) or movement of the entire cell during embryonic
There are some 20 different families of receptor proteins, each with morphogenesis or the chemotactic extravascular migration of leuko-
several isoforms responding to different ligands. The great majority of cytes during homing. Examples of highly developed and specialized
these receptors are transmembrane proteins. Members of each family functions of the cytoskeleton include the contraction of the sarcomere
share structural features that indicate either shared ligand-binding char- in striated muscle cells and the bending of the axoneme of cilia and
acteristics in the extracellular domain or shared signal transduction flagella.
properties in the cytoplasmic domain, or both. There is little relationship The catalogue of cytoskeletal structural proteins is extensive and still
either between the nature of a ligand and the family of receptor proteins increasing. The major filamentous structures found in non-muscle cells
to which it binds and activates, or the signal transduction strategies by are microfilaments (7 nm thick), microtubules (25 nm thick) and inter-
which an intracellular response is achieved. The same ligand may acti- mediate filaments (10 nm thick). Other important components are pro-
vate fundamentally different types of receptor in different cell types. teins that bind to the principal filamentous types to assemble or
Cell surface receptor proteins are generally grouped according to disassemble them, regulate their stability or generate movement. These
their linkage to one of three intracellular systems: ion channel-linked include actin-binding proteins such as myosin, which in some cells can
receptors; G-protein coupled receptors; or receptors that link to enzyme assemble into thick filaments, and microtubule-associated proteins.
systems. Other receptors do not fit neatly into any of these categories. Pathologies involving cytoskeletal abnormalities include ciliopathies
All the known G-protein-coupled receptors belong to a structural (resulting from the abnormal assembly and function of centrioles, basal
group of proteins that pass through the membrane seven times in a bodies and cilia); neurodegenerative diseases (a consequence of defec-
series of serpentine loops: these receptors are thus known as seven-pass tive anterograde transport of neurotransmitters along microtubules in
transmembrane receptors or, because the transmembrane regions are axons); and sterility (determined by defective or absent microtubule-
formed from α-helical domains, as seven-helix receptors. The best associated dynein in axonemes, e.g. Kartagener's syndrome).
known of this large group of phylogenetically ancient receptors are the
odorant-binding proteins of the olfactory system; the light-sensitive Actin filaments (microfilaments)
receptor protein, rhodopsin; and many of the receptors for clinically Actin filaments are flexible filaments, 7 nm thick (Fig. 1.13A). Within
useful drugs. A comprehensive list of receptor proteins, their activating most cell types, actin constitutes the most abundant protein and in
ligands and examples of the resultant biological function is given in some motile cells its concentration may exceed 200 μM (10 mg protein
Pollard et al (2016). per ml cytoplasm). The filaments are formed by the ATP-dependent
polymerization of actin monomer (with a molecular mass of 43 kDa)
Major signalling pathways into a characteristic string of beads in which the subunits are arranged
Most cell surface receptors stimulate intracellular target enzymes to in a linear tight helix with a distance of 13 subunits between turns
transmit and amplify a signal upon ligand binding. A signalling (Dominguez 2010). The polymerized filamentous form is termed
pathway can activate a series of intracellular targets located downstream F-actin (filamentous actin) and the unpolymerized monomeric form is
of the receptor, in particular the activity of intracellular proteins, or, like known as G-actin (globular actin). Each monomer has an asymmetric
neurotransmitter receptors, control the flow of water (aquaporins) and structure. When monomers polymerize, they confer a defined polarity
electrolytes across ligand-gated ion channels located on the plasma on the filament: the plus or barbed end favours monomer addition,
membrane. An amplified signal can be propagated to the nucleus to and the minus or pointed end favours monomer dissociation.
regulate gene expression in response to an external cell stimulus. Treadmilling designates the simultaneous polymerization of an
The cyclic adenosine monophosphate (cAMP) pathway is a major actin filament at one end and depolymerization at the other end to
intracellular signalling pathway. For example, there is an increase in the maintain its constant length.
intracellular concentration of cAMP when adrenaline (epinephrine) See Bray (2001) for further reading.
binds to its receptor. Adrenaline breaks down glycogen into glucose
before muscle contraction. cAMP is formed from ATP by the action of Actin-binding proteins
the enzyme adenylyl cyclase and degraded to adenosine monophos- A wide variety of actin-binding proteins are capable of modulating the form
phate (AMP) by the enzyme cAMP phosphodiesterase. This mechanism of actin within the cell. These interactions are fundamental to the organiza-
led to the concept of a first messenger (adrenaline) mediating a cell- tion of cytoplasm and to cell shape. The actin cytoskeleton is organized as
signalling effect by a second messenger, cAMP. closely packed parallel arrays of actin filaments forming bundles or cables,
Signalling pathways play important roles in embryonic and fetal or loosely packed criss-crossed actin filaments forming networks (Fig.
development, body axis patterning, cell migration and cell prolifera- 1.14A). Actin-binding proteins hold together bundles and networks of actin
tion. They all contain components subject to diverse regulatory steps filaments. Actin-binding proteins can be grouped into G-actin (monomer)
and crosstalk mechanisms and some use different downstream effectors binding proteins and F-actin (polymer) capping, cross-linking and severing
activated by specific transcription factors. The following signalling path- proteins. Actin-binding proteins may have more than one function.
ways have clinical relevance: the JAK–STAT, Hedgehog (Hh), Wingless Capping proteins bind to the ends of the actin filament either to
(Wnt) and transforming growth factor (TGF)-β signalling pathways. For stabilize an actin filament or to promote its disassembly (see Fig. 1.13A).
example, erythropoietin stimulates the development of the erythroid Cross-linking or bundling proteins tie actin filaments together in
lineage (red blood cell formation) in bone marrow by a mechanism longitudinal arrays to form bundles, cables or core structures. The
that involves the JAK–STAT pathway (Fig. 1.11). bundles may be closely packed in microvilli and filopodia, where paral-
lel filaments are tied tightly together to form stiff bundles orientated in
Cytoskeleton the same direction. Cross-linking proteins of the microvillus actin
bundle core include fimbrin and villin.
The cytoskeleton is a three-dimensional network of filamentous Other actin-bundling proteins form rather looser bundles of fila-
intracellular proteins of different shapes, sizes and composition ments that run antiparallel to each other with respect to their plus and
distributed throughout the cytoplasm. It provides mechanical minus ends. They include myosin II, which can form cross-links with
support, maintains cell shape and rigidity, and enables cells to adopt ATP-dependent motor activity, and cause adjacent actin filaments to
highly asymmetric or irregular profiles. It plays an important part in slide on each other in the striated muscle sarcomere, and either change
establishing structural polarity and different functional domains the shape of cells or (if the actin bundles are anchored into the cell
within a cell. It also provides mechanical support for permanent membrane at both ends), maintain a degree of active rigidity. Filamin
projections from the cell surface (see below), including persistent interconnects adjacent actin filaments to produce loose filamentous
microvilli and cilia, and transient processes, such as the thin finger- gel-like networks composed of randomly orientated F-actin.
like protrusions called filopodia (0.1–0.3 μm) and lamellipodia F-actin can branch. The assembly of branched filamentous actin
(0.1–0.2 μm). Filopodia consist of parallel bundles of actin fila- networks involves a complex of seven actin-related proteins 2/3
ments and have a role in cell migration, wound healing and neurite (Arp2/3) that is structurally similar to the barbed end of actin.
growth. The protrusive thin and broad lamellipodia, found at the See Rotty et al (2013) for further reading.
leading edge of a motile cell, contain a branched network of actin Branched actin generated by the Arp2/3 protein complex localizes at
filaments. the leading edge of migrating cells, lamellipodia and phagosomes
The cytoskeleton restricts specific structures to particular cellular loca- (required for the capture by endocytosis and phagocytosis of particles
tions. For example, the Golgi apparatus is near the nucleus and endoplas- and foreign pathogens by immune cells). Formin can elongate pre-exist-
12 mic reticulum, and mitochondria are near sites of energy requirement. ing actin filaments by removing capping proteins at the barbed end.
 1
Basic structure and function of cells

CHAPTER
The adrenaline receptor is linked to adenylyl cyclase by G protein, The Wingless (Wnt) signalling pathway (Fig. 1.12B) relies on Wnt
which stimulates cyclase activity upon adrenaline binding. In the adren- proteins controlling tissue organization and body-axis formation
aline-dependent regulation of glycogen metabolism, the intracellular during embryogenesis and the regulation of stem cells in adult tissue.
signalling effects of cAMP are mediated by the enzyme cAMP-depen- Wnt protein binding to FZD (frizzled) receptor is regulated by several
dent protein kinase (or protein kinase A). In its inactive form, protein interacting proteins, including leucine-rich repeat containing G protein-
kinase A is a tetramer composed of two regulatory subunits (to which coupled receptor (Lgr) 5 or 6; R-spondin (Rspo) 1 to 4 and E3 ubiquitin
cAMP binds) and two catalytic subunits. Binding of cAMP results in the ligase enzyme (Znrf3 or Rnf43). In the absence of Rspos, the ubiquitin
dissociation of the catalytic subunits. Free catalytic subunits can phos- ligase catalyses FZD degradation, thus preventing Wnt protein binding.
phorylate serine residues on target proteins (Fig. 1.10). Rspo prevents enzyme activity, FZD receptors accumulate and Wnt
This pathway links a protein with tyrosine kinase activity (JAK) to a signalling increases. β-catenin then translocates to the nucleus and
transcription factor (STAT) that becomes activated by this event. STAT stimulates the transcription of Wnt target genes by interacting with the
(Signal Transducers and Activators of Transcription) proteins are tran- co-activators LEF1 (Lymphoid Enhancer-binding Factor 1) and TCF (T
scription factors with an SH2 domain. They are present in the cyto- Cell Factor) 1, TCF3 and TCF4 (not shown in Fig. 1.12B). In the
plasm in an inactive state. Stimulation of a receptor by ligand binding β-catenin independent pathway, Wnt protein induces G protein-cou-
recruits STAT proteins, which bind to the cytoplasmic portion of the pled phosphatidylinositol to activate protein kinase C (PKC). Wnt sig-
receptor-associated JAK protein tyrosine kinase through their SH2 nalling has direct implications for regenerative medicine and
domain and become phosphorylated. Phosphorylated STAT proteins Wnt-associated cancers. Regeneration, in contrast to repair, is a steady-
then dimerize and translocate into the nucleus, where they activate the state condition, for example of the normal epidermis and the gastroin-
transcription of target genes (Fig. 1.11). testinal lining. The possibility of restoring function to damaged tissue
The Hh signalling pathway (Fig. 1.12A) is involved in switching Gli following disease, injury or ageing depends on its capacity for tissue
(Glioma) factors from transcriptional repressors into activators in the repair.
cytoplasm to allow Hh-specific transcriptional events. Hh proteins bind TGF-β signalling is associated with the bone morphogenetic protein
to the receptor PTCH1 (PaTCHed Homologue 1) and then signal (BMP) signalling pathway (Fig. 1.12C). BMPs are members of the
through SMO (SMOothened), a transmembrane protein, to regulate TGF-β superfamily and regulate cell growth, differentiation and devel-
gene transcription by repressing or activating Gli3, the transcription opment in a wide range of biological processes by activating SMAD
factor. If SMO is not present, Sufu (SUppressor of FUsed) permits the transcription factor proteins.
truncated Gli3 repressor to block Hh-specific gene expression. If SMO is BMP/TGF-β ligands induce the dimerization and then heteromer-
present, activated full-length Gli2A translocates to the cell nucleus to ization of serine/threonine receptor kinases and phosphorylation of
regulate Hh-specific gene expression (the expression of cyclin D, cyclin the cytoplasmic signalling molecules SMAD2 and SMAD3 for the
E, Myc and Patched). Hh ligands include Sonic (Shh), Indian (Ihh) and TGF-β pathway, or SMAD1/5/8 for the BMP pathway. The common
Desert (Dhh). Dysfunctions of the Hh signalling pathway include Gorlin SMAD4 transducer translocates to the nucleus. Activated SMADs regu-
syndrome, basal cell carcinoma in the skin and medulloblastoma. late several biological processes by cell-specific modulation of tran-
scription. TGF-β is a tumour suppressor of premalignant cells but
enhances invasion and metastasis of more advanced carcinomas.
Mutations of SMAD4 genes are frequent in gastrointestinal and pan-
creatic tumours. For further reading on cell signalling pathways, see
Kierszenbaum and Tres (2019).
Septins are emerging as a novel cytoskeletal element because of their
Signalling molecule or ligand filamentous organization and association with actin filaments and
Receptor (hormone or growth factor) microtubules. They are guanosine triphosphate (GTP)-binding proteins
that form hetero-oligomeric complexes (see Mostowy and Cossart 2012
Adenylyl cyclase Plasma membrane
for additional information).

γ GTP
β
α α ATP Ligand binding
Inactive G protein Activated G protein
cAMP
Regulatory subunit Plasma membrane JAK STAT

cAMP-dependent
protein kinase (protein Catalytic subunit
kinase A)
Phosphodiesterase
degrades cAMP SH domain
Activated catalytic subunit
enters the nucleus Inactive STAT Inactive STAT

Nuclear envelope Phosphorylated

Cytoplasm (activated) STAT dimer
Nuclear envelope
Cytoplasm
Nucleus
CREB
CRE Nucleus
Gene activity
DNA
Gene activity
DNA
Fig. 1.10 The cAMP signalling pathway. Ligand binding to a cell receptor
leads to the activation of adenylyl cyclase by the guanosine triphosphate
(GTP)-bound G protein subunit to form cAMP from ATP. cAMP, the second
messenger, binds to the regulatory subunits of cAMP-dependent protein
kinase (protein kinase A) and releases the catalytic subunits. cAMP is Fig. 1.11 The JAK–STAT signalling pathway. Ligand binding to a receptor
eventually degraded by a cAMP-dependent phosphodiesterase. The leads to the attachment of the inactive transcription factor STAT, present
activated catalytic subunit translocates into the nucleus and phosphorylates in the cytosol, to the receptor-associated JAK protein tyrosine kinase via
the transcription factor CREB (CRE-binding protein) bound to the cAMP their SH2 domains. Phosphorylated STAT dimerizes and translocates to the
response element (CRE): specific gene expression of inducible genes nucleus where it activates transcription of target genes (With permission
occurs. (With permission from Kierszenbaum AL, Tres LL Histology and Cell from Kierszenbaum AL, Tres LL Histology and Cell Biology: An Introduction
Biology: An Introduction to Pathology, 5th ed. Elsevier. Copyright 2019.) to Pathology, 5th ed. Elsevier. Copyright 2019.) 12.e1
1
SECTION CELLS, TISSUES AND SYSTEMS

A Hedgehog signalling pathway

Patched homologue 1 Hedgehog (Hh)

(PTCH1) receptor Smoothened (SMO)

Suppressor
Full-length of fused
Gli2 A Gli3
activated Gli2A (Sufu)

Cleaved transcription
factor Gli3 (Glioma)
repressor
Nucleus

B Wingless (Wnt) signalling pathway

Frizzled (FZD) receptor Wnt protein

* Interacting protein

Phosphatidylinositol

β-catenin β G-protein

Protein kinase Cδ (PKCδ)

* (1) Lipoprotein receptor-related protein 5

(Lgr5) or Lgr6
Nucleus (2) R-spondin (Rspo 1 to 4)
(3) E3 ubiquitin ligase (Znrf3 or Rnf43)

C Transforming growth factor-β (TGF-β) signalling / Bone morphogenetic protein

(BMP) signalling pathway

Heterotetramer of type I
and type II Ser/Thr BMP/TGF-β ligands
kinase receptors

TGF-β SMAD2, SMAD3 P P P

SMAD1, SMAD5 or SMAD8 SMAD1, SMAD5 or SMAD8

BMP SMAD4 SMAD

complex
formation

Nucleus

Fig. 1.12 A, The Hedgehog (Hh) signalling pathway. Hh proteins bind to the receptor PTCH1 and then signal through
SMO, a transmembrane protein, to regulate gene transcription by repressing or activating Gli3, a transcription factor. If
SMO is not present, Sufu permits the truncated Gli3 repressor to block Hh-specific gene expression. If SMO is present,
activated full-length Gli2A translocates to the cell nucleus to regulate Hh-specific gene expression. Hh ligands include
Sonic (Shh), Indian (Ihh) and Desert (Dhh) hedgehog proteins. B, The Wingless (Wnt) signalling pathway. Wnt protein
binding to FZD receptor is regulated by interacting proteins (*): Leucine-rich repeat containing G protein-coupled receptor
(Lgr) 5 or 6; R-spondin (Rspo) 1 to 4 and E3 ubiquitin ligase enzyme (Znrf3 or Rnf43). In the absence of Rspos, the
ubiquitin ligase catalyses FZD degradation and so prevents Wnt protein binding. Rspo prevents enzyme activity, FZD
receptors accumulate and Wnt signalling increases; β-catenin translocates to the nucleus and stimulates the transcription
of Wnt target genes. C, The transforming growth factor-β (TGF-β) signalling/Bone morphogenetic protein (BMP) signalling
pathway. BMP/TGF-β ligands induce the dimerization and then heteromerization of serine/threonine receptor kinases
and phosphorylation of the cytoplasmic signalling molecules SMAD2 and SMAD3 for the TGF-β pathway, or SMAD1/5/8
for the BMP pathway. The common SMAD4 transducer translocates to the nucleus. Activated SMADs regulate several
biological processes by cell-specific modulation of transcription. (With permission from Kierszenbaum AL, Tres LL
Histology and Cell Biology: An Introduction to Pathology, 5th ed. Elsevier. Copyright 2019.)

12.e2
 1
Basic structure and function of cells

CHAPTER
This polarity can be visualized in negatively stained images by allow- (barbed) end to grow faster and then dissociates from the actin fila-
ing F-actin to react with fragments containing the active head region of ment. In addition, profilin participates in the conversion of ADP back
myosin. Myosins bind to filamentous actin at an angle to give the to the ATP–G-actin bound form. Thymosin β4 binds to the ATP–G-actin
appearance of a series of arrowheads pointing towards the minus end bound form, preventing polymerization by sequestering ATP–G-actin
of the filament, with the barbs pointing towards the plus end. into a reserve pool.
It involves the addition of ATP-bound G-actin monomers at the Members of the F-actin capping protein family are heterodimers
barbed end (fast-growing plus end) and removal of ADP-bound G-actin consisting of an α subunit (CPα) and a β subunit (CPβ) that cap the
at the pointed end (slow-growing minus end). Actin filaments grow or barbed end of actin filaments within all eukaryotic cells. Gelsolin has
shrink by addition or loss of G-actin monomer at both ends. Essentially, a dual role: it severs F-actin and caps the newly formed barbed end,
actin polymerization in vitro proceeds in three steps: nucleation (aggrega- blocking further filament elongation.
tion of G-actin monomers into a 3–4-monomer aggregate), elongation Fascin is an additional cross-linking protein. Villin is also a severing
(addition of G-actin monomers to the aggregate) and a dynamic steady protein, causing the disassembly of actin filaments and the collapse of
state (treadmilling). Specific toxins (e.g. cytochalasins, phalloidins and the microvillus.
lantrunculins) bind to actin and affect its polymerization. Cytochalasin In the presence of activated nucleation promotion factors, such as
D blocks the addition of new G-actin monomers to the barbed end of Wiskott–Aldrich syndrome protein (WASP) and WASP family verprolin-
F-actin; phalloidin binds to the interface between G-actin monomers in homologous protein (WAVE, also known as SCAR), the Arp2/3 protein
F-actin, thus preventing depolymerization; and lantrunculin binds to complex binds to the side of an existing actin filament (mother fila-
G-actin monomers, blocking their addition to an actin filament. ment) and initiates the formation of a branching actin daughter fila-
Profilin and thymosin β4 are G-actin binding proteins. Profilin ment at a 70° angle relative to the mother filament utilizing G-actin
binds to G-actin bound to ATP; it inhibits addition of G-actin to the delivered to the Arp2/3 complex site.
slow-growing (pointed) end of F-actin but enables the fast-growing

12.e3
 1
Basic structure and function of cells

CHAPTER
Monomer Tubulin dimer Tetramer Fig. 1.13 Structural and molecular
features of cytoskeletal components.
G-actin–ATP A, The actin filament (F-actin) is a
β-tubulin GTP
7 nm thick polymer chain of ATP-
α-tubulin GTP
bound G-actin monomers. F-actin
ATP
consists of a barbed (plus) end,
the initiation site of F-actin, and a
pointed (minus) end, the dissocia-
Plus end tion site of F-actin. F-actin can be
severed and capped at the barbed
Barbed end
end by gelsolin. B, The microtubule
is a 25 nm diameter polymer of
Unit length filament GTP-bound α-tubulin and GTP-
bound β-tubulin dimers. The dimer
assembles at the plus end and
depolymerizes at the minus end. A
linear chain of α-tubulin/β-tubulin
dimers is called a protofilament. In
the end-on (top) view, a microtubule
7 nm thick 25 nm in diameter displays 13 concentrically arranged
tubulin subunits. C, Tetrameric
complexes of intermediate filament
subunits associate laterally to form
Intermediate filament a unit length filament consisting
of eight tetramers. Additional unit
length filaments anneal longitudinally
and generate a mature 10 nm thick
intermediate filament.
Severed actin filament Minus end

Gelsolin
Capped barbed end Protofilament

10 nm thick

Pointed end
Top view:
13 concentric tubulins

A Actin filament B Microtubule C Intermediate filament

Other classes of actin-binding protein link the actin cytoskeleton to of known subtypes of myosin II; they assemble in different ways and
the plasma membrane either directly or indirectly through a variety of have different dynamic properties. In skeletal muscle the myosin mol-
membrane-associated proteins. The latter may also create links via ecules form bipolar filaments 15 nm thick. Because these filaments have
transmembrane proteins to the extracellular matrix. Best known of a symmetric antiparallel arrangement of subunits, the midpoint is bare
these is the family of spectrin-like molecules, which can bind to actin of head regions. In smooth muscle the molecules form thicker, flattened
and also to each other and to various membrane-associated proteins to bundles and are orientated in random directions on either face of the
create supportive networks beneath the plasma membrane. Tetramers bundle. These arrangements have important consequences for the con-
of spectrin α and β chains line the intracellular side of the plasma tractile force characteristics of the different types of muscle cell.
membrane of erythrocytes and maintain their integrity by their associa- Related molecules include the myosin I subfamily of single-headed
tion with short actin filaments at either end of the tetramer. molecules with tails of varying length. Functions of myosin I include
Class V myosins (see below) are unconventional motor proteins trans- the movements of membranes in endocytosis, filopodial formation in
porting cargoes (such as vesicles and organelles) along actin filaments. neuronal growth cones, actin–actin sliding and attachment of actin to
Class I myosins are involved in membrane dynamics and actin organiza- membranes as seen in microvilli. As indicated above, molecular motors
tion at the cell cortex, thus affecting cell migration, endocytosis, pinocy- of the myosin V family are implicated in the movements of cargoes on
tosis and phagocytosis. Tropomyosin, an important regulatory protein of actin filaments. So, for example, myosin Va transports vesicles along
muscle fibres, is also present in non-muscle cells, where its function may F-actin tracks in a similar manner to kinesin and cytoplasmic dynein-
be primarily to stabilize actin filaments against depolymerization. related cargo transport along microtubules. Each class of motor protein
has different properties, but during cargo trafficking they often function
Myosins, the motor proteins together in a coordinated fashion. (See Hammer and Sellers 2012 for
The myosin family of microfilaments is often classified within a distinct further reading on class V myosins.)
category of motor proteins. Myosin proteins have a globular head
region consisting of a heavy and a light chain. The heavy chain bears Other thin filaments
an α-helical tail of varying length. The head has an ATPase activity and A heterogeneous group of filamentous structures with diameters of
can bind to and move along actin filaments – the basis for myosin 2–4 nm occurs in various cells. The two most widely studied forms, titin
function as a motor protein. The best-known class is myosin II, which and nebulin, constitute around 13% of the total protein of skeletal
occurs in muscle and in many non-muscle cells. Its molecules have two muscle (Ch. 5). They are amongst the largest known molecules and
heads and two tails, intertwined to form a long rod. The rods can bind have subunit weights of around 106; native molecules are about 1 μm
to each other to form long, thick filaments, as seen in striated and in length. Their repetitive bead-like structure gives them elastic proper-
smooth muscle fibres and myoepithelial cells. Myosin II molecules can ties that are important for the effective functioning of muscle, and
also assemble into smaller groups, especially dimers, which can cross- possibly for other cells.
link individual actin microfilaments in stress fibres and other F-actin
arrays. The ATP-dependent sliding of myosin on actin forms the basis Microtubules
for muscle contraction and the extension of microfilament bundles, as Microtubules are polymers of tubulin with the form of hollow, rela-
seen in cellular motility or in the contraction of the ring of actin and tively rigid cylinders, approximately 25 nm in diameter and of varying
myosin around the cleavage furrow of dividing cells. There are a number length (up to 70 μm in spermatozoan flagella). They are present in most 13
 1
Basic structure and function of cells

CHAPTER
Spectrin-related molecules are present in many other cells. For proteins to integral plasma membrane proteins such as integrins
instance, fodrin is found in neurones and dystrophin occurs in muscle (directly or indirectly), and thence to focal adhesions (consisting of a
cells, linking the contractile apparatus with the extracellular matrix via bundle of actin filaments attached to a portion of a plasma membrane
integral membrane proteins. Proteins such as ankyrin (which also binds linked to the extracellular matrix).
actin directly), vinculin, talin, zyxin and paxillin connect actin-binding

13.e1
1
SECTION CELLS, TISSUES AND SYSTEMS

axis in straight rows of alternating α- and β-tubulins, forming protofila-

ments (Fig. 1.13B). Typically, 13 protofilaments (the number can vary
between 11 and 16) associate in a ring to form the wall of a hollow
cylindrical microtubule (Fig. 1.14C). Each longitudinal row is slightly
out of alignment with its neighbour, so that a spiral pattern of alternat-
ing α and β subunits appears when the microtubule is viewed from the
side. There is a dynamic equilibrium between the dimers and assembled
microtubules: dimeric asymmetry creates polarity (α-tubulins are all
orientated towards the minus end, β-tubulins towards the plus end).
Tubulin is added preferentially to the plus end; the minus end is rela-
tively slow-growing. Microtubules frequently grow and shrink at a rapid
and constant rate, a phenomenon known as dynamic instability, in
which growing tubules can undergo a ‘catastrophe’, abruptly shifting
from net growth to rapid shrinkage. The primary determinant of
whether microtubules grow or shrink is the rate of GTP hydrolysis.
Tubulins are GTP-binding proteins; microtubule growth is accompa-
A nied by hydrolysis of GTP, which may regulate the dynamic behaviour
of the tubules. Microtubule growth is initiated at specific sites, the
microtubule-organizing centres, of which the best known are centro-
somes (from which most cellular microtubules polymerize) and the
centriole-derived basal bodies (from which cilia grow). Microtubule-
organizing centres include a specialized tubulin isoform known as
γ-tubulin that is essential for the nucleation of microtubule growth.
Various drugs (e.g. colcemid, vinblastine, griseofulvin, nocodazole)
cause microtubule depolymerization by binding the soluble tubulin
dimers and so shifting the equilibrium towards the unpolymerized
state. Microtubule disassembly causes a wide variety of effects, including
the inhibition of cell division by disruption of the mitotic spindle.
Conversely, the drug paclitaxel (taxol) is a microtubule depolymeriza-
tion inhibitor because it stabilizes microtubules and promotes abnor-
mal microtubule assembly. Although this can cause a peripheral
neuropathy, paclitaxel is widely used as an effective chemotherapeutic
agent in the treatment of breast and ovarian cancer.
B
Microtubule-associated proteins
Various proteins that can bind to assembled tubulins may be concerned
with structural properties or associated with motility. One important
class of microtubule-associated proteins (MAPs) consists of proteins
that associate with the plus ends of microtubules. They regulate the
dynamic instability of microtubules as well as interactions with other
A cellular substructures. Structural MAPs form cross-bridges between adja-
cent microtubules or between microtubules and other structures such
as intermediate filaments, mitochondria and the plasma membrane.
Microtubule-associated proteins found in neurones include: MAPs 1A
and 1B, which are present in neuronal dendrites and axons; MAPs 2A
S and 2B, found chiefly in dendrites; and tau, found only in axons. MAP
4 is the major microtubule-associated protein in many other cell types.
Structural microtubule-associated proteins are implicated in microtu-
bule formation, maintenance and disassembly, and are therefore of
considerable significance in cell morphogenesis, mitotic division, and
the maintenance and modulation of cell shape.
C Transport-associated microtubule-associated proteins are found in
situations in which movement occurs over the surfaces of microtubules,
Fig. 1.14 The cytoskeleton. A, An immunofluorescence micrograph of α-actin e.g. cargo transport, bending of cilia and flagella, and some movements
microfilaments (green) in human airway smooth muscle cells in culture. of mitotic spindles. They include a large family of motor proteins, the
The actin-binding protein, vinculin (red), is localized at the ends of actin best known of which are the dyneins and kinesins. Another protein,
filament bundles; nuclei are blue. B, An immunofluorescence micrograph dynamin, is involved in endocytosis. The kinetochore proteins assem-
of keratin intermediate filaments (green) in human keratinocytes in culture. ble at the chromosomal centromere during mitosis and meiosis. They
Desmosome junctions are labelled with antibody against desmoplakin attach (and thus fasten chromosomes) to spindle microtubules; some
(red). Nuclei are stained blue (Hoechst). C, An electron micrograph of of the kinetochore proteins are responsible for chromosomal move-
human nerve showing microtubules (small, apparently hollow structures ments in mitotic and meiotic anaphase.
in cross-section, long arrow) in a transverse section of an unmyelinated All of these microtubule-associated proteins bind to microtubules
axon (A), engulfed by a Schwann cell (S). Neuronal intermediate filaments and either actively slide along their surfaces or promote microtubule
(neurofilaments) are the solid, electron-dense profiles, mainly in transverse assembly or disassembly. Kinesins and dyneins can simultaneously
section (short arrow). (A, Courtesy of Dr T Nguyen, Professor J Ward, Dr attach to membranes such as transport vesicles and convey them along
SJ Hirst, King's College London. B, Courtesy of Professor Dr WW Franke, microtubules for considerable distances, thus enabling selective target-
German Cancer Research Centre, Heidelberg. C, Courtesy of Dr Bart ing of materials within the cell. Such movements occur in both direc-
Wagner, Histopathology Department, Sheffield Teaching Hospitals, UK.) tions along microtubules. Kinesin-dependent motion is usually towards
the plus ends of microtubules, e.g. from the cell body towards the axon
terminals in neurones, and away from the centrosome in other cells.
cell types, being particularly abundant in neurones, leukocytes and Conversely, dynein-related movements are in the opposite direction, i.e.
blood platelets. Microtubules are the predominant constituents of the to the minus ends of microtubules. The transport of cargoes along
mitotic spindles of dividing cells and also form part of the axoneme of microtubules is the means by which neurotransmitters are delivered
cilia, flagella and centrioles. along axons within synaptic vesicle precursors towards neuronal syn-
Microtubules consist of tubulin dimers and microtubule-associated apses (anterograde axonal transport, utilizing kinesins) and membrane-
proteins. There are two major classes of tubulin: α- and β-tubulins. bound vesicles are returned for recycling to the neuronal soma
Before microtubule assembly, tubulins are associated as dimers with a (retrograde axonal transport, utilizing dyneins).
combined molecular mass of 100 kDa (50 kDa each). Each protein Dyneins also form the arms of peripheral microtubules in cilia and
14 subunit is approximately 5 nm across and is arranged along the long flagella, where they make dynamic cross-bridges to adjacent microtubule
 1
Basic structure and function of cells

CHAPTER
pairs. When these tethered dyneins try to move, the resulting shearing meiosis instead of mitosis, lack centrioles). See Gönczy (2012) for
forces cause the axonemal array of microtubules to bend, generating further reading on the structure and assembly of the centriole. They
ciliary and flagellar beating movements. Kinesins form a large and usually lie close together, at right angles or, most usually, at an oblique
diverse family of related microtubule-stimulated ATPases. Some kinesins angle to each other (an arrangement often termed a diplosome), within
are motors that move cargo and others cause microtubule disassembly, the centrosome, a densely filamentous region of cytoplasm at the centre
whilst still others cross-link mitotic spindle microtubules to push the of the cell. The centrosome is the major microtubule-organizing centre
two centriolar poles apart during mitotic prophase. See Bray (2001) for of most cells; it is the site at which new microtubules are formed and
further reading. the mitotic spindle is generated during cell division.
Centriole biogenesis is a complex process (Fig. 1.16) At the begin-
Centrioles, centrosomes and basal bodies ning of the S phase (DNA replication phase) of the cell cycle (see
Centrioles are microtubular cylinders 0.2 μm in diameter and 0.4 μm below), a new daughter centriole forms at right-angles to each separated
long (Fig. 1.15). They are formed by a ring of nine microtubule triplets maternal centriole. Each mother–daughter pair forms one pole of the
linked by a number of other proteins. At least two centrioles occur in next mitotic spindle, and the daughter centriole becomes fully mature
all animal cells that are capable of mitotic division (eggs, which undergo only as the progeny cells are about to enter the next mitosis. Because
centrosomes are microtubule-organizing centres, they lie at the centre
of a network of microtubules, all of which have their minus ends proxi-
mal to the centrosome.
The microtubule-organizing centre contains complexes of γ-tubulin
that nucleate microtubule polymerization at the minus ends of micro-
tubules. Basal bodies are microtubule-organizing centres that are closely
T
related to centrioles, and are believed to be derived from them. They
are located at the bases of cilia and flagella, which they anchor to the
cell surface. The outer microtubule doublets of the axoneme of cilia and
flagella originate from two of the microtubules in each triplet of the
basal body.
Intermediate filaments
Intermediate filaments are about 10 nm thick and are formed by a
heterogeneous group of filamentous proteins. In contrast to actin fila-
ments and microtubules, which are assembled from globular proteins
with nucleotide-binding and hydrolysing activity, intermediate fila-
L
ments consist of filamentous monomers lacking enzymatic activity.
Intermediate filament proteins assemble to form linear filaments in a
three-step process. First, a pair of intermediate filament protein sub-
units, each consisting of a central α-helical rod domain of about 310
amino acids flanked by head and tail non-α-helical domains of vari-
able size, form a parallel dimer through their central α-helical rod
domains coiled around each other. The variability of intermediate fila-
ment protein subunits resides in the length and amino-acid sequence
of the head and tail domains, thought to be involved in regulating
the interaction of intermediate filaments with other proteins. Second,
a tetrameric unit is formed by two antiparallel half-staggered coiled
dimers. Third, eight tetramers associate laterally to form a 16 nm thick
Fig. 1.15 A duplicated pair of centrioles in a human carcinoma specimen. unit length filament (ULF). Individual ULFs join end to end to form
Each centriole pair consists of a mother and daughter, orientated approxi- short filaments that continue growing longitudinally by annealing to
mately at right angles to each other so that one is sectioned transversely other ULFs and existing filaments. Filament elongation is followed by
(T) and the other longitudinally (L). The transversely sectioned centrioles internal compaction leading to the 30 nm thick intermediate filament
are seen as rings of microtubule triplets (arrow). (Courtesy of Dr Bart (Figs 1.13C, 1.14B). The tight association of dimers, tetramers and
Wagner, Histopathology Department, Sheffield Teaching Hospitals, UK.) ULFs provides intermediate filaments with high tensile strength

Fig. 1.16 A centriolar pair consists of a

mother and a daughter centriole that dupli-
‘New’ mother/new daughter and At mitosis, centrosomes cates once every cell cycle in preparation
‘old’ mother/new daughter have a complete pericentriolar for cell division. Each centriole generates a
centrioles are fully assembled at protein complement daughter centriole, which means that there
the end of the G2 phase
are two new daughter centrioles. The previ-
Mitotic spindle ous daughter centriole becomes the ‘new’
G2 mother and the previous mother centriole
remains as the ‘old’ mother centriole, i.e.
an ‘old’ mother centriole is connected to
Mitosis
one of the new daughter centrioles and
a ‘new’ mother centriole is linked to the
Pericentriolar
material other new daughter centriole. (Adapted with
permission from Kierszenbaum AL, Tres LL
Histology and Cell Biology: An Introduction to
Pathology, 5th ed. Elsevier. Copyright 2019.)
S Daughter
Cytokinesis centriole

G1
Mother
centriole
During the G1–S phase During the G1 phase, a cell has one centrosome consisting of
transition, centrosomes two centrioles (a mother centriole and a daughter centriole)
duplicate. Daughter surrounded by pericentriolar material
centrioles arise from
each centriole
15
 1
Basic structure and function of cells

CHAPTER
The association of membrane vesicles with dynein motors means provide a means of targeting Golgi vesicular products to different parts
that certain cytomembranes (including the Golgi apparatus) concen- of the cell.
trate near the centrosome. This is relevant because the microtubules

15.e1
1
SECTION CELLS, TISSUES AND SYSTEMS

and resistance to stretching, compression, twisting and bending forces. protein components. The INM contains its own specific integral mem-
In contrast to actin filaments and microtubules, intermediate fila- brane proteins (lamin B receptor and emerin, both providing binding
ments are non-polar (because of the antiparallel alignment of the sites for chromatin bridging proteins). A mutation in the gene encoding
initial tetramers) and do not bind nucleotides (as in G-actin and emerin causes X-linked Emery–Dreifuss muscular dystrophy (EDMD),
tubulin dimers), and ULFs anneal end to end to each other (in con- characterized by skeletal muscle wasting and cardiomyopathy.
trast to the polarized F-actin and microtubules, with one end, the plus The nuclear lamina, a 15–20 nm thick, protein-dense meshwork, is
end, growing faster than the other end, the minus end). See Herrmann associated with the inner face of the INM. The major components of
et al (2007) for further reading. the nuclear lamina are lamins, the type V intermediate filament proteins
Intermediate filaments are found in different cell types and are often consisting of A-type and B-type classes.
present in large numbers, either to provide structural strength where it The nuclear lamina reinforces the nuclear membrane mechanically,
is needed (see Figs 1.14B, 1.14C) or to provide scaffolding for the attach- determines the shape of the nucleus and provides a binding site for a
ment of other structures. Intermediate filaments form extensive cytoplas- range of proteins that anchor chromatin to the cytoskeleton. Nuclear
mic networks extending from cage-like perinuclear arrangements to the lamin A, with more than 350 mutations, is the most mutated protein
cell surface. Intermediate filaments of different molecular classes are linked to human disease. These are referred to as laminopathies, charac-
characteristic of particular tissues or states of maturity and are therefore terized by nuclear structural abnormalities that cause structurally weak-
important indicators of the origins of cells or degrees of differentiation, ened nuclei, leading to mechanical damage. Lamin A mutations cause a
as well as being of considerable value in histopathology. surprisingly wide range of diseases, from progeria to various dystrophies,
Intermediate filament proteins have been classified into five distinct including an autosomal dominant form of EDMD. A truncated farnesyl-
types on the basis of their primary structure and tissue-specific expres- ated form of lamin A, referred to as progerin, leads to defects in cell
sion. Of the different classes of intermediate filaments, keratin (cyto- proliferation and DNA damage of mesenchymal stem cells and vascular
keratin) proteins are found in epithelia, where keratin filaments are smooth muscle cells. Affected patients display cardiovascular disease and
always composed of equal ratios of type I (acidic) and type II (basic to die at an early age. Mice lacking lamin B1 and lamin B2 survive until
neutral) keratins to form heteropolymers. About 20 types of each of the birth; however, neuronal development is compromised when lamin B1
acidic and basic/neutral keratin proteins are known. For further reading or lamin B2 is absent. Overexpression of lamin B1 is associated with
on keratins in normal and diseased epithelia, see Pan et al (2012). autosomal dominant leukodystrophy characterized by gradual demyelin-
Within the epidermis, expression of keratin heteropolymers changes as ation in the central nervous system. See Worman (2012) and Burke and
keratinocytes mature during their transition from basal to superficial Stewart (2013) for additional reading on lamins and laminopathies.
layers. Genetic abnormalities of keratins are known to affect the Condensed chromatin (heterochromatin) tends to aggregate near the
mechanical stability of epithelia. For example, the disease epidermolysis nuclear envelope during interphase. At the end of mitotic and meiotic
bullosa simplex is caused by lysis of epidermal basal cells and blistering prophase (see below), the lamin filaments disassemble by phosphoryla-
of the skin after mechanical trauma. Defects in genes encoding keratins tion, causing the nuclear membranes to vesiculate and disperse into the
5 and 14 produce cytoskeletal instability leading to cellular fragility in endoplasmic reticulum. During the final stages of mitosis (telophase),
the basal cells of the epidermis. When keratins 1 and 10 are affected, proteins of the nuclear periphery, including lamins, associate with the
cells in the spinous (prickle) cell layer of the epidermis lyse, and this surface of the chromosomes, providing docking sites for membrane
produces the intraepidermal blistering of epidermolytic hyperkeratosis. vesicles. Fusion of these vesicles reconstitutes the nuclear envelope,
See Porter and Lane (2003) for further reading. including the nuclear lamina, following lamin dephosphorylation. See
Type III intermediate filament proteins, including vimentin, desmin, Simon and Wilson (2011) for further reading on the nucleoskeleton.
glial fibrillary acidic protein and peripherin, form homopolymer inter- The transport of molecules between the nucleus and the cytoplasm
mediate filaments. Vimentin is expressed in mesenchyme-derived cells occurs via specialized nuclear pore structures that perforate the nuclear
of connective tissue and some ectodermal cells during early develop- membrane (Fig. 1.17A). They act as highly selective directional molecu-
ment; desmins in muscle cells; glial fibrillary acidic protein in glial cells; lar filters, permitting proteins such as histones and gene regulatory
and peripherin in peripheral axons. Type IV intermediate filaments proteins (which are synthesized in the cytoplasm but function in the
include neurofilaments, nestin, syncoilin and α-internexin. nucleus) to enter the nucleus, and molecules that are synthesized in the
Neurofilaments are a major cytoskeletal element in neurones, particu- nucleus but destined for the cytoplasm (e.g. ribosomal subunits, trans-
larly in axons (see Fig. 1.14C), where they are the dominant protein. fer RNAs and messenger RNAs) to leave the nucleus.
Neurofilaments (NF) are heteropolymers of low (NF–L), medium Ultrastructurally, nuclear pores appear as disc-like structures with an
(NF–M) and high (NF–H) molecular weight (the NF–L form is always outer diameter of 130 nm and an inner pore with an effective diameter
present in combination with either NF–M or NF–H forms). Abnormal for free diffusion of 9 nm (Fig. 1.17B). The nuclear envelope of an active
accumulations of neurofilaments (neurofibrillary tangles) are character- cell contains up to 4000 such pores. The nuclear pore complex has an
istic features of a number of neuropathological conditions. Nestin octagonal symmetry and is formed by an assembly of more than 50
resembles a neurofilament protein, which forms intermediate filaments proteins, the nucleoporins. The inner and outer nuclear membranes fuse
in neurectodermal stem cells in particular. The type V intermediate fila- around the pore complex (see Fig. 1.17A). Nuclear pores are freely per-
ment group includes the nuclear lamins A, lamin B1 and lamin B2 lining meable to small molecules, ions and proteins up to about 17 kDa. See
the inner surface of the nuclear envelope of all nucleated cells. Lamin C Raices and D'Angelo (2012) for further reading on nuclear pore complex
is a splice variant of lamin A. Lamins provide a mechanical framework composition. Most proteins that enter the nucleus do so as complexes
for the nucleus and act as attachment sites for a number of proteins that with specific transport receptor proteins known as importins. Importins
organize chromatin at the periphery of the nucleus. They are unusual in shuttle back and forth between the nucleus and cytoplasm. Binding of
that they form an irregular anastomosing network of filaments rather the cargo to the importin requires a short sequence of amino acids known
than linear bundles. See Burke and Stewart (2013) for further reading. as a nuclear localization sequence (NLS), and can either be direct or take
place via an adapter protein. Interactions of the importin with compo-
Nucleus nents of the nuclear pore move it, together with its cargo, through the
pore by an energy-independent process. A complementary cycle func-
The nucleus (see Figs 1.1–1.2) is generally the largest intracellular struc- tions in export of proteins and RNA molecules from the nucleus to the
ture and is usually spherical or ellipsoid in shape, with a diameter of cytoplasm using transport receptors known as exportins.
3–10 μm. Conventional histological stains, such as haematoxylin or A small GTPase called Ras-related nuclear protein (Ran) regulates
toluidine blue, detect the acidic components (phosphate groups) of the import and export of proteins across the nuclear envelope.
deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in cells and For further reading on the Ran pathway and exportins/importins,
tissue sections. DNA and RNA molecules are said to be basophilic see Clarke and Zhang (2008) and Raices and D'Angelo (2012).
because of the binding affinity of their negatively charged phosphate
groups to basic dyes such as haematoxylin. A specific stain for DNA is Chromatin
the Feulgen reaction. DNA is organized within the nucleus in a DNA–protein complex known
as chromatin. The protein constituents of chromatin are the histones and
Nuclear envelope the non-histone proteins. Non-histone proteins are an extremely hetero-
The nucleus is surrounded by the nuclear envelope, which consists of an geneous group that includes structural proteins, DNA and RNA polymer-
inner nuclear membrane (INM) and an outer nuclear membrane (ONM), ases, and gene regulatory proteins. Histones are the most abundant
separated by a 40–50 nm perinuclear space that is spanned by nuclear group of proteins in chromatin, primarily responsible for the packaging
pore complexes (NPCs). The perinuclear space is continuous with the of chromosomal DNA into its primary level of organization, the nucleo-
lumen of the endoplasmic reticulum. The ONM has multiple connec- some. There are four core histone proteins – H2A, H2B, H3 and H4 –
16 tions with the endoplasmic reticulum, with which it shares its membrane which vary in amino acid sequence and post-translational modifications
 1
Basic structure and function of cells

CHAPTER
A-type lamins include lamin A (interacting with emerin), lamin C, B1 and lamin B2 (expressed in somatic cells), and testis-specific lamin
lamin C2 and lamin AΔ10 encoded by a single gene (LMNA). Lamin A B3. Lamin B1 is encoded by the LMNB1 gene; lamin B2 is encoded by
and lamin C are the major A-type lamins expressed in somatic cells, the LMNB2 gene.
whereas lamin C2 is expressed in testis. B-type lamins include lamin

16.e1
Another random document with
no related content on Scribd:
 An originellen G e r ä t h e n besitzen die Wafiomi nur wenige.
Eisensachen und Kalebassen werden meist aus Irangi bezogen,
Körbe aus Gras selbst geflochten. Die Töpfe sind ziemlich schlecht,
am Halse manchmal mit Zebrafell benäht. Zur Aufnahme der Milch
dienen hölzerne Gefässe, die sich ähnlich auch in Ukerewe und am
Ostufer des Victoria-See finden.
Als Wa ff e n dienen Wurfspeere mit eingelassener Spitze und
lederne Rundschilde, sowie zur Jagd Bogen und vergiftete Pfeile.
Der
Verkehr mit der
Aussenwelt
beschränkt
sich auf den
Milchgefäss der
mit den Wafiomi.
Wataturu und
Wambugwe. Ueber Uassi gelangen die
Industrieartikel aus Irangi nach Ufiomi
und Iraku. Früher zogen Leute aus Irangi
direkt nach Iraku, um Granaten, die dort
Topf der Wafiomi. häufig vorkommen und in Irangi als
Ohrschmuck getragen werden, zu kaufen.
Wasukuma und andere Wanyamwesi kommen behufs Vieh- und
Elfenbeinhandel manchmal ins Land.
Die Si t t e n der Wafiomi sind eigenartig, wenn auch vielfach
durch Bantugebräuche beeinflusst. Die Beschneidung und das
Ausbrechen bezw. Vorbiegen der Zähne wird bei beiden
Geschlechtern erst beim Reifwerden vorgenommen. Bei Mädchen
findet dann ein besonderes Fest statt, bei welchem mit der
nebenstehend abgebildeten Klapper gerasselt wird. Dann bleibt das
Mädchen ein Jahr im Tembe in einem von den Männern gesonderten
Raum. Sie darf keine Nahrung berühren und wird von anderen
Weibern gefüttert und getränkt, auch darf sie ihr Haar nicht
scheeren. Zur Nachtzeit jedoch verlässt sie das Tembe und tanzt mit
jungen Männern.[18]
Will ein junger Mann heirathen,
so schickt er dem Vater der
Auserwählten Pombe, dessen
Annahme als Einwilligung gilt. Das
Brautgeld besteht gewöhnlich aus
drei Ziegen und einem Spaten; ist
der Bräutigam jedoch arm, so
braucht er nur Pombe und Honig
zu bringen. Vielweiberei ist
allgemein üblich. Die Geschlechter
nehmen ihre Mahlzeiten getrennt
ein. Die Arbeiten sind so ziemlich
gleich auf Mann und Weib vertheilt,
welch' letztere sich auch am
Klapper, Wafiomi. Ackerbau betheiligen. Eine
unbeliebte Frau wird dem Vater zurückgeschickt. Heirathet sie
wieder, so gehört das erste Kind dem Manne der ersten Ehe, das
zweite dem der zweiten, das dritte wieder dem der ersten Ehe u. s.
w. bis zum achten Kind, worauf alle Kinder dem Manne aus zweiter
Ehe gehören, ein höchst merkwürdiger und seltsamer Gebrauch. Die
Wafiomi heirathen meist im Stamme, selten Wambugwe-Weiber,
doch werden Wafiomi-Weiber oft von Wambugwe und Wataturu zur
Ehe genommen.
Will jemand ein Haus bauen, so ist ihm die ganze Nachbarschaft
dabei behilflich, die Männer errichten das Holzwerk und tragen die
Graslagen auf, die Weiber schütten den Lehm auf's Dach.
Eine grosse Rolle spielt der Z a u b e r d o kto r, der »Regen macht«
und bei Krankheiten Amulettzauber, seltener Pflanzenmedizin
anwendet. Schneidet sich jemand zufällig, so gilt dies als sehr böses
Zeichen und es wird sofort ein Schaf erwürgt und der Betreffende mit
dem Mageninhalt bespritzt, was überhaupt als Friedenszauber gilt.
Man glaubt an natürlichen Tod und Tod durch Zauberei, doch hat
letzterer nichts im Gefolge. Ein Verstorbener wird in Ufiomi kauernd
mit Fell und Ledersandalen vor dem Tembe beerdigt. In Iraku, wo
ich, um Schädel zu sammeln, mehrmals Gräber öffnete, waren
dieselben ebenfalls stets vor den Temben und bestanden aus 2 m
tiefen Schächten, von deren Sohle ein Seitenschacht ausging, in
welchem der Todte auf einem Brett stets mit Lederzeug und
Sandalen bestattet war.
Den Geistern der Verstorbenen bringt man Todtenopfer von
Pombe; auch werden ihnen zu Ehren Tänze aufgeführt, bei welchen
eine kleine gestielte Trommel gerührt wird, die ganz jener der
Wapare gleicht. Ein Gottesbegriff ist vorhanden, Gebete sind jedoch
nicht gebräuchlich.
Die Bewohner benachbarter Distrikte führen keine Kriege
untereinander, sondern prügeln sich nur mit ihren langen Stöcken.
Den Krieg nach Aussen beschliesst der Zauberdoktor, der auch
Anführer desselben ist. Der Kampf besteht in Gefechten auf freiem
Felde, selbst im Siegesfall dringen die Kämpfer nicht in Feindesland
ein. Männliche Kriegsgefangene werden nicht getödtet, sondern zur
Auslösung aufbewahrt, laufen jedoch meist davon. Die Wafiomi
halten keine Sklaven, wurden jedoch mehrmals von den Ober-
Aruschanern (zuletzt 1891) behufs Sklavenraub angefallen und es
sollen sich in Ober-Aruscha Wafiomi-Sklaven befinden.
In Streitfällen entscheiden die Aeltesten. Diebstahl im eigenen
Land ist unerhört und sehr schimpflich, Fremde zu bestehlen gilt als
ehrenvoll. Mord wird durch Blutgeld gesühnt, nur wenn letzteres
nicht geleistet wird tritt Blutrache ein. Ausständige Schulden tilgt der
Gläubiger durch selbstständige Pfändung. Grund und Boden gilt
niemals als Besitz, nur die darauf stehenden Feldfrüchte sind
Eigenthum, das vom Nachbarfeld abgegrenzt wird. Daher kann
Jeder unbeackertes, wenn auch früher bebaut gewesenes Land
bestellen und erhält dadurch Recht auf die Ernte. Ebenso kann Vieh
überall weiden.
Sternschnuppen gelten als böses Zeichen, der Mond und die
Jahreszeiten geben die Zeiteintheilung.
Das G e sa mmt b il d der Wafiomi ist das eines noch völlig
unberührten, im Grunde gut gearteten Naturvolkes. Bei den traurigen
Erfahrungen, die sie von ihren Nachbarn, besonders den Massai
gemacht, ist es nicht verwunderlich, dass sie bisher allen Fremden
feindlich gegenüber standen, doch wird es zweifellos gelingen, sie in
dieser Hinsicht zugänglicher zu machen. Wurde mir als erstem
Weissen in dem berüchtigten Ufiomi doch wenigstens kein
feindlicher, in Iraku sogar ein harmlos freundlicher Empfang zu theil.
Sobald die Wafiomi vor feindlichen Einfällen gesichert und nicht
mehr gezwungen sind, sich gleich wilden Thieren in Erdhöhlen zu
verbergen, werden sie sicher ihre Eigenschaften als treffliche
Ackerbauer noch weiter entfalten und zur Besiedelung der herrlichen
noch unbewohnten Plateauländer beitragen. Ob sie freilich zu einer
höheren Kulturmission geeignet erscheinen, ist bei dem
konservativen Sinn und der völligen, bis zur Verwahrlosung
getriebenen Bedürfnisslosigkeit dieses Volkes fraglich. Auch ist es
nicht wahrscheinlich, dass sie einem stärkeren Eindringen des
Bantu-Elementes widerstehen werden.
Vorläufig nehmen die Ba n tu vö l ke r, jener Hauptstamm Mittel-
Afrika's, im abflusslosen Gebiet noch keinen grossen Raum ein. Das
bedeutendste Volk sind jedenfalls die Wa g o g o, die schon von
mehreren Reisenden beschrieben worden sind und auf die ich schon
deshalb nicht näher eingehe, weil ich nur wenige Vertreter dieses
Stammes kennen gelernt. Die Wanyamwesi dagegen, deren
Wohngebiet besonders in den Zweigstamm der Wakimbu ins
abflusslose Gebiet übergreift, und die viele Ansiedelungen in
demselben besitzen, sollen an anderer Stelle Erwähnung finden. Wir
wenden uns daher gleich den nördlich, in direkter Nachbarschaft der
Wafiomi lebenden Warangi und Wambugwe zu.
Die Stämme der Wa mb u g we und Wa r a n g i gehören, obwohl
räumlich ziemlich getrennt lebend, doch einer Gruppe an, ja sie
bilden thatsächlich nur e i n e n Stamm. Da jedoch die Warangi durch
ihren starken Verkehr mit Fremden, sei es Küstenleuten, sei es
Wagogo und Wanyamwesi, viel von ihrer Ursprünglichkeit verloren
haben, so wird nachfolgend hauptsächlich von den Wambugwe die
Rede sein.
Die Wambugwe bewohnen ein sehr beschränktes Gebiet. Ihre
Wohnstätten, die Temben, sind in der baumlosen Salzebene am
Südende des Manyara-See verstreut, welche, eine alte Fortsetzung
des Sees bildend, zur Regenzeit theilweise mit Salzwasser
überschwemmt ist und nur stellenweise spärlichen Graswuchs
gedeihen lässt. Die Felder liegen südlich und östlich von dieser
Ebene in fruchtbarerem Gebiet. Die Warangi hausen in den
hügelartigen Landschaften, welche sich bei der Araber-
Niederlassung Kondoa (Irangi) ausdehnen, sowie nordöstlich davon
in Tandala. Die ebenfalls zu Irangi gehörigen Distrikte Uassi und
Burunge haben keine Warangi- sondern Wafiomi-Bevölkerung.
Ihre Abkunft leiten die Wambugwe von Irangi, also aus dem
Süden her; doch ist es zweifellos, dass ihre Einwanderung schon vor
vielen Generationen erfolgte. Ihrer Sprache nach sind die
Wambugwe ein Bantu-Volk und gehören möglicherweise mit den
Wagogo einer Gruppe an. Doch scheint es sicher, dass sie viele
fremde Elemente, vor allem Wataturu und Wafiomi, in sich
aufgenommen haben. Immerhin weist der Stamm, wie er sich uns
heute darstellt, physisch ein ziemlich einheitliches Gepräge auf.
Die Wambugwe sind mittelgrosse schlanke und kräftige Leute
von oft tadellosen Körperformen. Die Gesichtszüge bilden ein
Mittelding zwischen hamitischen und reinem Negertypus; der
nebenstehend abgebildete Häuptling Mbi zeigt dieselben in
besonders charakteristischer Weise. Die Hautfarbe hat
vorherrschend chokoladebraune, rothbraune bis gelbliche Töne,
besonders unter den Weibern trifft man hellfarbige, ungemein
zierliche Gestalten. Die Haltung ist eine freie und stolze, der
Gesichtsausdruck intelligent.
 Diesem Aeusseren
entspricht auch der
Ch a r a kt e r, der den
Mbugwe vor allem zum
Krieger stempelt. Von drei
Seiten von ungeheuren
Steppenländern, auf der
vierten vom Steilabfall des
Plateaus begrenzt, ist das
Umbugwe-Ländchen von
allen Seiten den Einfällen
feindlicher Stämme, vor
allen der Massai und Ober-
Aruschaner ausgesetzt.
Während die umwohnenden
Stämme, wie die Wataturu
und Wafiomi unter diesen
Einfällen schwer litten und Wambugwe-Häuptling Mbi.
ihr ganzes Vieh an die
Massai verloren, wussten die Wambugwe trotz der ungünstigen,
völlig offenen Lage ihres Ländchens sich doch alle Feinde vom
Halse zu halten und ihre kostbarste Habe, ihr Rindvieh, zu
vertheidigen. So verächtlich der Massai auch über die meisten
»Mangati« (Ackerbauer-Feinde) denkt, den Ltoroto, wie er die
Wambugwe nennt, kann er seine Achtung nicht versagen. Denn gar
oft haben die wilden Viehräuber der Steppe sich blutige Köpfe in
Umbugwe geholt, ja mehrmals kehrten die Wambugwe den Spiess
um, sie fielen ihrerseits im Massailande ein, erstürmten die Kraals
am Donyo Kissale und trieben das Vieh weg.
Die Erfahrungen, welche sie seit jeher gemacht, mussten dazu
beitragen, die Wambugwe misstrauisch gegen alles Fremde zu
machen. Mehrmals wurden Handelskarawanen von der Küste, die in
völlig harmloser Absicht kamen, von ihnen überfallen, ausgeraubt
und fast vollständig aufgerieben, so dass jahrelang sich Niemand als
die unerschrockenen Elephantenjäger nach Umbugwe wagte. Auch
diese schwebten fortwährend in Lebensgefahr und waren allerlei
Uebergriffen von Seiten der Eingeborenen ausgesetzt.
Auch mir, dem ersten Europäer den sie sahen, wollten die
Wambugwe in gleicher Weise begegnen, doch bekam ihnen dies
schlecht: zum ersten Mal empfingen die nie Besiegten eine
empfindliche Niederlage. Doch gerade ihr Verhalten nach derselben
zeigt von dem klaren Verstand der Wambugwe. Während andere
Stämme, wenn ihr Angriff abgeschlagen ist, sich meist in alle Winde
verlieren, gänzlich unerreichbar sind und den nächsten Europäer der
durch ihr Gebiet kommt wieder anfallen, erkannten die Wambugwe
sofort, dass sie einer überlegenen Macht gegenüberstanden. Es
kam zu einer Verständigung und die Schonung der Verwundeten und
Auslieferung der Kriegsgefangenen meinerseits trug nicht wenig zur
Befestigung der neuen Freundschaft bei. Fast ein Jahr später fand
ich die Wambugwe gänzlich umgewandelt als friedliche, zugängliche
Leute und Küstenkarawanen sowohl wie andere Reisende, die nach
mir das Land besuchten, fanden die beste Aufnahme.
Wenn wir das Ae u sse r e der Wambugwe betrachten, so finden
wir, dass dieselben sich von der Alles überfluthenden Massai-Mode
ziemlich unabhängig gehalten haben (Abb. Taf. 4 und pag. 22). Die
S ta mme sma r ke bei Männern und Weibern besteht aus einem von
der Nasenwurzel über die Wangen verlaufenden Schnitt. Das
Haupthaar tragen sie entweder abrasirt oder sorgfältig in ganz kleine
Zöpfchen geflochten. Kleine Holzstücke oder einige Glasperlen
dienen als Schmuck der Ohren. Die jungen Männer pflegen auf
Reisen und auf der Jagd nackt zu gehen, sonst besteht die
K le id u n g aus einem Lendenschurz oder Mantel von ungemein
weich und biegsam gegerbtem Leder, welches mit Glasperlen
verziert und gelb, braun oder roth gefärbt wird. Zeug wird, seit das
Land erschlossen ist, immer mehr getragen. Die Weiber bekleiden
sich mit einem Lendenschurz aus Leder. An den Beinen werden
häufig Eisendraht und Glasperlen getragen, an den Füssen schöne
mit Glasperlen verzierte Ledersandalen. Die Beschneidung ist
üblich. Als Kriegsschmuck tragen die jungen Leute häufig einen
Büschel Federn in den Haaren.
Die Wo h n u n g e n der Wambugwe (Abb. pag. 18) bestehen aus
quadratischen, nach den Weltgegenden orientirten Temben, die in
Entfernungen von 30-40 m von einander in der Ebene verstreut sind.
Dieselben sind ungleich gross und haben von 6-50 m im Geviert,
dienen jedoch selten mehr als einer Familie zum Aufenthalt. Trotz
ihrer oft bedeutenden Ausdehnung sind die Temben nur brusthoch.
Die Seitenwände bestehen aus Stangen mit Lehmverkleidung, das
flache Dach, welches das ganze Tembe bedeckt, besitzt eine
Unterlage von Stangen aus dem festen Kernholz der Dumpalmen,
auf welchen eine Schicht quergelegter Sorghumstengel und die
Lehmauflage folgt. In der Mitte der Dachfläche wird manchmal eine
Stange als Zierrath aufgestellt. Die grösseren, besonders die
Häuptlingstemben haben an der (westlichen) Vorderseite ein 1½ m,
an den übrigen ½ m breites Vordach. Der Innenraum dient als
Aufenthalt für Menschen und Vieh. Die kleineren Temben bestehen
aus einem einzigen Raume mit vielen Dachstützen und höchstens
einer Einzäunung für das Vieh, die grösseren aus mehreren, durch
Wände getrennten Wohnstätten. Bei ihrer Niedrigkeit, der darin
herrschenden absoluten Dunkelheit und den unzähligen Stangen
und Verschlagwänden sowie dem Stalldunst, bieten die Temben
gerade keinen behaglichen Aufenthalt, um so weniger als es darin
von kleinen Zecken, den sogenannten Papassi, wimmelt.
Die Warangi haben dieselben, doch weniger gut gebauten
Temben, dieselben liegen jedoch nicht einzeln, sondern zu drei oder
vier, einen kleinen Hof umschliessend, der gegen Aussen durch
einen Knüppelzaun abgesperrt ist.
 Die Ja g d spielt bei den Wambugwe eine ziemlich grosse Rolle
und wird mit dem Wurfspeer, seltener mit Bogen und Pfeil ausgeübt.
Fischfang wird nur zu Zeiten grosser Hungersnoth im Kwoufluss
betrieben.
Weit wichtiger ist die Vie h zu ch t, die allerdings durch die
Seuche stark gelitten hat, immerhin aber noch recht bedeutend ist.
Das Mbugwe-Rind ist ein echtes Zebu mit starkem Höcker, kräftiger,
untersetzter Gestalt und meist kurzen Hörnern. Es ist verschieden,
braun, schwarz und grau gefärbt, auch Blässen sind nicht selten.
Wie bei den meisten afrikanischen Rindern, ist der Milchertrag ein
geringer, e in Liter täglich gilt schon als ganz gute Leistung. Die
Rinder grasen durchweg in der Salzebene um die Temben herum
und verlassen deren Umkreis niemals. Obwohl sie anscheinend nur
spärliche Weide finden, gedeihen sie doch vortrefflich und sind von
seltener Ausdauer und Zähigkeit. Ich hatte Umbugwe-Rinder
während meiner ganzen Reise mit und dieselben vertrugen das kalte
Plateauklima ebensogut wie Hitze und Wassermangel in der Steppe,
ja selbst die starken Märsche ermüdeten sie keineswegs. Die
Wambugwe pflegen ihre Rinder durch Einschnitte in die Ohren zu
bezeichnen.
Unter den Rindern treiben sich in der weiten Ebene des
Dorfgebietes zahlreiche, halbwilde Ese l herum. Dieselben sind
kräftig gebaut, haben eine glänzend silbergraue Farbe und sehr oft
leichte Streifung an den Beinen, erinnern also lebhaft an den wilden
Esel der Somali-Länder. Sie werden nur zum Herbeitragen von
Feuerholz, das sehr weit hergeholt werden muss, benutzt, laufen
aber meist frei umher. Auch die Esel fand ich, sobald sie gezähmt
sind, was rasch gelingt, sehr ausdauernd. An Kleinvieh werden viele
Ziegen und Schafe, an Geflügel Hühner gehalten. Hunde und
auffallend viele Katzen sind überall zu finden.
Der Acke r b a u wird nicht im Tembegebiet getrieben, weil
dasselbe in der Regenzeit oft von Lachen überschwemmt ist und
auch als Viehweide dient. Dadurch wird den Wambugwe das Leben
ziemlich sauer gemacht. Wenn sie Trinkwasser oft eine Stunde weit
holen müssen, so werden Feldfrüchte mehrere, Brennholz oft sogar
viele Stunden weit hergeholt. Die Aecker liegen südlich und östlich
vom Tembegebiet und sind gut gehalten. Angebaut wird fast nur
Sorghum weisser und rother Varietät, letzterer ausschliesslich zur
Bier-(Pombe)-Bereitung, sowie Tabak. Trotz des anscheinend wenig
fruchtbaren Bodens ist das Erträgniss doch ein ungemein reiches,
wie man an den kolossalen Getreidevorräthen sehen kann, welche
die Wambugwe in meterhohen und ebenso breiten, cylindrischen
Strohkörben in ihren Hütten aufspeichern.
Die Ha u p tn a h r u n g ist
der Sorghumbrei. Um
diesen herzustellen, wird
der Sorghum am Dach des
Tembe aufgebreitet, hierauf
meist unenthülst zwischen
Mahlsteinen zerrieben.
Nicht selten mischt man
Tembe der Warangi. dem Mehl Salz vom
Balangda-See (Mangati)
bei, manchmal sogar das scharfe, für Nicht-Wambugwe gänzlich
ungeniessbare Salz des Manyara. Das Fleisch aller Thiere wird
genossen, nur Fisch, Nashorn und Elephant gelten als unrein und
werden nur während einer Hungersnoth verzehrt. Betreffs des
Zusammenessens von Männern und Weibern bestehen keine
bestimmten Vorschriften. Hirsebier (Pombe) wird in sehr grossen
Mengen hergestellt, in mächtigen Töpfen gähren gelassen und dann
getrunken. Tabak wird besonders von Männern geraucht, geschnupft
und gekaut, in letzterem Falle wird ihm das scharfe Salz des
Manyara beigemengt.
TAFEL XX
 Meisenbach, Riffarth & Co. Berlin heliogr.

HIRT AUS UFIOMI

 Die G e r ä t h e der Wambugwe zeichnen sich vielfach durch
Zierlichkeit aus. Dem Ackerbau dient eine breitklingige Hacke, die,
wie alle Eisengeräthe, aus Irangi-Eisen gefertigt, ja oft direkt von dort
importirt wird, da die Warangi-Schmiede mit Recht als geschickt
gelten. Ausser den grossen, früher erwähnten Vorrathskörben,
dienen als Gefässe kleine Körbe und Kalebassen, die vielfach aus
Irangi importirt und mit hübschen schwarzen Ornamenten versehen
sind. Die netten Töpfe und Krüge werden von eigenen Handwerkern
gefertigt und gehören nicht der Hausindustrie an. Erwähnung
verdient das Gerben der Rindshäute, zu welchem Behufe die Haut
getrocknet, mit einem besonderen Beil abgekratzt und mit Fett und
Kuhmist eingerieben wird. Sie wird dann einen Tag ausgebreitet, mit
menschlichem Urin begossen, dann geknetet und zwei Tage in Urin
gelagert. Hierauf wird sie nochmals ausgebreitet, getrocknet und
abgerieben. Durch dieses Verfahren bekommt die Haut eine
erstaunliche, sammetartige Weiche. Wünscht man das Leder zu
färben, so wird die betreffende Pflanzenfarbe dem Urin beigemischt.
Die Wa ff e n der Wambugwe bestehen aus Speer, Schild, Bogen,
Pfeil und Schleuder. Schwerter scheinen vollkommen unbekannt.
Der Speer ist ein echter Wurfspeer mit ziemlich breiter Klinge,
eingelassenem Schaftdorn, lederbenähtem Hals und mit Eisen
umwundenem Schaftende. Jeder Krieger trägt zwei bis vier Speere
in der Rechten. In der Linken führt er den spitzovalen Schild, welcher
aus Büffelhaut gefertigt, mit kleinen vorgetriebenen Buckeln
versehen ist und an der Hinterseite einen Längsstock besitzt, (Abb.
Tafel 4). Bogen und Pfeile sind leicht und dienen nur alten Leuten
und Kindern als Waffen und Jagdgeräth. Als solches für kleines Wild
dient auch die interessante Steinschleuder, ein Geräth, das man
sehr selten in Mittelafrika findet. (Abb. pag. 186.) Dieselbe wird auch
zum Verjagen der Vögel aus den Feldern gebraucht. Im Gebrauch
der Waffen, besonders im Werfen der Speere besitzen die
Wambugwe bedeutende Geschicklichkeit.
 Hacke der Wambugwe.

Kalebassen-Ornamente der Wambugwe.

 Die Speere der Warangi sind zierlicher, doch weniger kräftig, ihre
Schilde meist kreisrund mit Mittelbuckel.
Von einem Ha n d e l konnte in Umbugwe kaum die Rede sein,
bevor das Erscheinen meiner Expedition eine neue Aera für das
Land eröffnete. Küstenkarawanen wagten sich, wie gesagt, nicht ins
Land, und selbst Wasukuma kamen nur selten dahin. Der Verkehr
mit der Aussenwelt beschränkte sich auf das Eintauschen von Irangi-
Eisen und Mangati-Salz gegen Vieh; selten unternahmen die
Wambugwe einen Zug nach Meatu, um Irangi-Hacken gegen Häute
zu vertauschen. Das wenige, was sie an Glasperlen und Zeug
benöthigten, erhielten sie durch die Warangi, die stets ungehindert
im Lande verkehrten, seltener durch Wagogo der nördlichen
Distrikte, die manchmal bis Umbugwe vordringen.
Gegenwärtig freilich durchziehen häufig Europäer- und Swahíli-
Karawanen das Land und eine vollständige Umwandlung aller
Lebensverhältnisse ist im Gange.
Ueber das merkwürdige in n e r e L e b e n dieses Stammes konnte
ich verhältnissmässig viel erfahren, da ich während meines zweiten
Aufenthaltes mit den Eingeborenen sehr freundschaftlich verkehrte
und vorzügliche Dolmetscher besass.
Die erste Erfahrung, welche der neugeborene Mbugwe an seinen
Landsleuten macht, ist keine angenehme. Es werden ihm nämlich
mit einem scharfen Messer zwei Schnitte über das Gesicht — die
S ta mme sma r ke — gezogen. Alle Wambugwe ohne Ausnahme
tragen diese; sieht man Jemand ohne die charakteristischen
Schnitte, so ist er entweder ein Fremder oder er wurde von seiner
Mutter nach Empfang besonderer Medizin, die durch den
Zauberdoktor verabreicht wird, geboren.
Die Namengebung erfolgt in der Kindheit durch Verwandte und
gilt fürs Leben. Nur wenn ein Kind krank wird, nimmt der
Zauberdoktor öfter an, dass ein verstorbener Verwandter (besonders
 der Vater) etwas gegen
dasselbe habe. Dann giesst
man dem Todten Pombe
aufs Grab und das Kind
nimmt dessen Namen als
zweiten an. Die
Beschneidung wird von
kundigen Personen bei
Männern und Weibern in der
Jugend vollzogen; dabei
findet ein Trinkgelage statt.
Das Reifwerden der
Mädchen giebt zu keinen Steinschleuder der
Gebräuchen Anlass. Wambugwe.
Sehr merkwürdig, ja unter Mittelafrikanern fast
vereinzelt ist das grundsätzliche Fehlen der
Vielweiberei. Selbst Häuptlinge haben nur eine
Frau, und als Kutadu, der kein Mbugwe, sondern ein
Mtaturu ist, dennoch eine zweite nahm, erregte dies
allgemeines Aergerniss. Die Brautwerbung
geschieht durch Uebersendung eines Rindes an
Speer der den Vater, wird dieses angenommen, so wird die
Warangi. Hochzeit durch Tanz und Pombegenuss gefeiert.
Einen weiteren Brautpreis hat der Bräutigam nicht zu zahlen, ja, es
ist üblich, dass der Vater der Tochter Rinder in die Ehe mitgiebt. Tritt
Scheidung ein, so muss der Gatte diese dem Schwiegervater
zurückgeben, dann können beide Theile wieder heirathen. Der
Verführer eines Mädchens muss dem Vater, der einer Frau dem
Gatten das etwa geborene Kind überlassen, weitere Streitigkeiten
entstehen deshalb nicht.
Heirathen mit Weibern fremder Stämme, wie Wafiomi, Wataturu
und besonders Warangi sind nicht selten und tragen dazu bei, den
Wambugwe hamitisches Blut zuzuführen. Kindsmord soll niemals
vorkommen.
Bei K r a n kh e it e n wird der Zauberdoktor gerufen, der
Pflanzenmedizin, gewöhnlich Brechmittel eingiebt. In schweren
Fällen nennt er die Person, die den Kranken bezaubert hat und die
stets gleichen Geschlechts mit diesem ist. Dann pflegen die
Verwandten dem Häuptling ein oder mehrere Rinder zu bringen und
in nächtlicher Berathung beschliesst dieser mit den
Stammesältesten den Zauberer zu tödten. Dieser wird dann
meuchlings niedergemacht.
Beim To d e eines Menschen wird der Rath des Zauberdoktors
nicht eingeholt. Man schlachtet eine Ziege und reibt mit deren Fett
die Augen des Verstorbenen ein, damit sein Geist die neugeborenen
Kinder nicht sehe und ihnen durch bösen Blick schade. Hierauf wird
die Leiche, wenn ein Mann, auf dem rechten, wenn eine Frau, auf
dem linken Arm liegend im Tembe begraben. Nur wer durch eine
Speerwunde stirbt wird draussen beerdigt. Beim Leichenschmaus
wird der erste Pombeschluck aufs Grab gespien. Dann wird das
Tembe ruhig weiter bewohnt.
Erscheint ein Todter im Traume, so wird der Zauberdoktor
befragt, der dann meist die Opferung eines schwarzen Stieres
fordert, dessen Nabel im Grabe verscharrt wird. —
Wie aus dem Obigem hervorgeht, spielt auch bei den
Wambugwe, wie bei allen Bantu der Ah n e n ku lt die erste Rolle. So
werden auch Löwe und Elephant als Geister längst Verstorbener
angesehen. Ein eigentlicher Gottesbegriff scheint jedoch zu fehlen.
Die Sklaverei ist in Umbugwe unbekannt, ihr kriegerischer Sinn
schützt die Wambugwe auch vor Sklavenjagden, welche die Ober-
Aruschaner nach diesen Gegenden zu unternehmen pflegen.
 Die ursprüngliche Re g i e r u n g sfo r m ist zweifellos die Familien-
Republik, wie sie heute noch im Distrikt Wabwa besteht. Die
ungeheure Macht der Zauberdoktoren, sowie die Erblichkeit dieser
Würde, liessen dieselben jedoch rasch zu kleinen Herrschern,
Häuptlingen, heranwachsen. Von den drei in Umbugwe lebenden
Häuptlingen ist nur Mbi ein echter Mbugwe, Mtakayko hat
Wataturublut und Kutadu ist ein reiner Mtaturu. Die beiden Letzteren
sind die mächtigsten und als Zauberer sehr gefürchtet, ihr reicher
Viehbesitz stammt fast nur von Geschenken her, die sie in dieser
Eigenschaft bekamen.
Zu ihren Künsten gehört vor Allem das Re g e n ma ch e n. Dazu
nimmt der Zauberer bei hellem Sonnenschein ein schwarzes Kalb
und ein schwarzes Schaf, hebt sie auf das Tembedach, schlitzt ihnen
den Bauch auf und spritzt den Mageninhalt nach allen Richtungen.
Dann giesst er Wasser und Medizin in ein Gefäss; ist der Zauber
gelungen, so kocht das Wasser auf und Regen erfolgt. Um Regen zu
hindern zieht sich der Zauberer in das Innere des Temberaumes
zurück und erhitzt einen Bergkrystall[19] in einer Kalebasse.
Die Macht des Häuptlings ist sehr durch die Aeltesten
beschränkt, die in allen wichtigen Angelegenheiten mitzusprechen
haben. Zu seinen Vorrechten gehört, dass er die Erlaubniss zum
Ernteschnitt giebt; am ersten Tage wird dann auf seinen Feldern
geschnitten.
Die Kr ie g e der Wambugwe untereinander sind wenig blutig.
Ziegen und Rinder werden dabei niemals fortgetrieben, als Beute
gelten nur Hausgeräth und Hühner. Ganz anders freilich wissen sie
sich gegen auswärtige Feinde zu vertheidigen. Als mächtiger
Kriegszauber wird ein Angehöriger des feindlichen Distriktes
abgefangen, getödtet, seine Haut abgezogen und an Armen und
Brust getragen. Als Friedenszeichen überreichen die Wambugwe
etwas Gras, das sie nach Massaiart vorher bespeien. Ihr
gewöhnlicher Gruss ist »Tálala«.
 Mord wird durch Blutrache gesühnt. Von Diebstählen werden nur
die grösseren dem Häuptling angezeigt. Dieser verbannt dann den
Dieb und zieht dessen Eigenthum ein, wobei die Aeltesten etwas,
der Bestohlene aber nichts abbekommt. Grundbesitz ist bekannt,
das urbar gemachte Land gilt endgiltig als erworben.
Sonne und Mond betrachten die Wambugwe als Brüder, die
Sterne als Menschen, deren einer stirbt, wenn eine Sternschnuppe
fällt.
Wenn wir das G e sa mmtb i l d der Wambugwe betrachten, so
finden wir einen körperlich und geistig gesunden, völlig urwüchsigen
Stamm, der nach jahrhundertelanger Abgeschlossenheit nun
plötzlich mit der Aussenwelt in regen Verkehr tritt. Es ist zweifellos,
dass die Veränderungen, welche dessen Lebensgewohnheiten
schon in den nächsten Jahren erleiden müssen äusserst tiefgehende
sein werden. Mir jedoch, der ich als erster Weisser die Wambugwe
in voller Ursprünglichkeit gesehen, der ich ihnen — hoffentlich als
letzter Europäer — in blutigem Kampfe gegenüberstand und sie
dann aber auch als Freunde kennen lernte; mir scheint es fast
sicher, dass dieser Stamm bei kräftiger und doch maassvoller
Behandlung zu einem der wichtigsten Kulturelemente Deutsch-
Ostafrika's heranzubilden wäre. —
Die Plateaulandschaften südwestlich vom Gurui-Berg, bis gegen
Ugogo hin, bewohnt ein anderer Bantu-Stamm, die Wa n ya tu r u, d.
i. Leute von Turu. Dieselben leiten ihre Abkunft vom Gurui-Berg her,
sind aber jedenfalls schon sehr alte Ansiedler. In vieler Hinsicht
weisen sie Aehnlichkeit mit den Waschaschi im östlichen Nyansa-
Gebiet, besonders aber mit deren ursprünglichsten Vertretern, den
Wakara von Ukara auf. Jedenfalls gehören die Wanyaturu zu den
tiefststehenden Bewohnern des abflusslosen Gebietes, was
besonders auffällt, wenn man aus dem Innern, aus Unyamwesi
kommt, wo die Kulturstufe eine ungleich höhere ist.
 Die Wanyaturu sind kräftige, hochgewachsene Leute, ziemlich
dunkelfarbig und von recht reinem Negertypus, der im Allgemeinen
dem der Wanyamwesi gleicht. (Abb. Taf. 13 und pag. 110.) An
Hamiten erinnernde Gesichtszüge sind selten und wohl nur bei
Nachkommen eingewanderter Wataturu zu finden. Die Männer
gehen vollkommen nackt und scheinen nicht das geringste
Schamgefühl zu kennen. Um die Hüften tragen sie zahlreiche,
festsitzende Bastschnüre, um die Knöchel Glasperlen oder
Lederschnüre. Beide Geschlechter sind beschnitten. Die Männer
tragen die Haare meist kurz, manchmal mit einer Feder am Scheitel.
Seltener drehen sie kleine Zöpfchen, die sie mit Fett festigen, oder
tragen, wie die Wanyairamba, dünne, lange Haarzöpfchen, die nach
hinten hängen. Die Weiber tragen Lederlendenschurze und rasiren
den Schädel, ältere Leute schlingen manchmal ein Stückchen Zeug
um die Hüften.
Die Wanyaturu gelten mit Recht als boshaft. Wildheit und Hass
alles Fremden bildet den Grundzug ihres Charakters der durch
politische Zerfahrenheit des Landes noch verschärft wird.
Ihre Wo h n u n g e n bestehen aus rechtwinkelig angeordneten,
etwa brusthohen und ca. 4 m breiten, sehr ärmlichen Temben. Der
rechte Winkel ist durch einen innen mit Stachelgestrüpp geschützten
niedrigen Zaun von buschigen Euphorbien abgeschnitten, wodurch
der dreieckige Viehhof gebildet ist. Manchmal zieht sich eine
Euphorbienhecke um einen Komplex solcher Temben. Das Innere
der Temben ist in dunkele, räucherige Kammern getheilt, der Boden
stellenweise vertieft. Neben den Temben graben sie unterirdische
Schutzlöcher, höhlen auch oft Baobabs aus um sich darin zu
verbergen.
Der Ac ke r b a u beschränkt sich auf Sorghum und Eleusine. An
Hausthieren werden Rinder, Ziegen, Schafe, Esel, Hühner und
Hunde gehalten. Sie gewinnen Salz aus dem Singisa-See, welches
sie den Wanyamwesi von Ussure verkaufen, sonst verkehren sie fast