EMBRYOLOGY &
MOLECULAR
EMBRYOLOGY
OVERVIEW
WEEK 1 (DAYS
1-6)
• Fertilization day 1
• Cleavage day 2-3
• Compaction day 3
• Formation of blastocyst day 4
• Ends with implantation day 6
FERTILIZATIO
N
• Fertilization the fusion of spermatozoa
with the mature ovum
• Capacitation enables the sperm cell to
interact with uterine cells
• Acrosome reaction important for
penetration of the spermatozoa through the
zona pellucida
THE EGG (AND CORONA RADIATA)
AT OVULATION
Corona radiata
Zona
pellucida
(ZP-1, -2,
and -3)
Cortical
granules
FERTILIZATION
Fertilization has 3 phases :
• Penetration of the Corona Radiata
• Penetration of the Zona Pellucida
• Fusion of the Oocyte and Sperm Cell
Membranes
– Cortical and zona reactions
– Resumption of the second meiotic
division
FERTILIZATION
The main results of fertilization are as follows:
• Restoration of the diploid number of
chromosomes
• Determination of the sex of the new
individual
• Initiation of cleavage
CLEAVAGE
Cleavage = cell division
Goals:
grow unicellular zygote to
multicellular embryo.
Divisions are slow:
12 - 24h
Cleavage begins about 24h after
pronuclear fusion
EMBRYO UNDERGOES COMPACTION : FIRST
DIFFERENTIATION OF EMBRYONIC
LINEAGES
• Caused by increased cell-cell adhesion
• Cells that are forced to the outside of the morula are
destined to become trophoblast cells that will form
placenta
• The inner cells will form the embryo proper and are called
the inner cell mass (ICM).
FORMATION OF THE
BLASTOCYST
Sodium channels appear on the surface of the outer trophoblast
cells sodium and water are pumped into the forming
blastocoele.
“HATCHING” OF THE
BLASTOCYST:
PREPARATION FOR
IMPLANTATION
Hatching of the embryo from the zona pellucida occurs just
prior to implantation.
WEEK 2 (DAYS 7-14)
IMPLANTATION
• Implanted embryo becomes more deeply
embedded in endometrium attachment,
apposition, and invasion process
• Further development of trophoblast into
placenta
• Development of a bi-laminar embryo,
amniotic cavity, and yolk sac.
IMPLANTATION AND
PLACENTATION (DAY 8)
Trophoblast further differentiates and invades maternal tissues
– Cytotrophoblast stem cell population
– Syncytiotrophoblast invasive fused cells (syncytium) derived from cytotrophoblast
– Breaks maternal capillaries trophoblastic lacunae fill with maternal blood
Inner cell mass divides into epiblast and hypoblast:
– Epiblast contributes to forming the overlying amniotic membrane and amniotic cavity
– Hypoblast contributes to forming the underlying yolk sac.
DAY 9 DAY 12-13
WEEK 3 (DAYS
14-21)
• Two layer germ disc
• Primitive streak forms
• Gastrulation forms tri-laminar embryo
• Neural induction
• Left-right asymmetry
GASTRUL
ATION
At gastrulation the two layered epiblast is converted
into the three primary embryonic germ layers:
– Ectoderm outside, surrounds other layers later
in development generates skin and nervous
tissue
– Mesoderm middle layer, generates most of the
muscle, blood and connective tissues of the body and
placenta
– Endoderm eventually most interior of embryo,
generates the epithelial lining and associated glands of
the gut, lung, and urogenital tracts
AT GASTRULATION, PRIMITIVE ENDODERM
IS REPLACED BY DEFINITIVE OR
EMBRYONIC ENDODERM THEN MESODERM
IS FORMED
MESODERM IS PATTERNED IN A CRANIAL TO
CAUDAL GRADIENT
Axial mesoderm passes
through the node and migrates along
the midline forms the notochord
Paraxial mesoderm passes
just caudal to the node and
migrates slightly laterally --> forms
cartilage, skeletal muscle, and
dermis
Lateral plate mesoderm
passes more caudal and migrates
more laterally forms
circulatory system and body
cavity linings.
Extraembryonic
mesoderm passes most
caudal and migrates most
laterally –forms extraembryonic
THE NODE ALSO SETS UP THE
NEURAL PLATE
LEFT-RIGHT ASYMMETRY IS
ESTABLISHED AT
GASTRULATION
Leftward beating of cilia at node moves
secreted molecules sonic hedgehog (Shh)
& FGF-8 to the left side of embryo.
Causes left side genes Nodal and Pitx2 to
be expressed which then pattern
developing organs.
If cilia are defective Shh and Fgf8 can
randomly end up on right side, resulting in
reversal of symmetry, aka situs inversus
(liver on the left, spleen on the right, etc.)
WHAT HAPPENS IF THERE IS “NOT ENOUGH”
GASTRULATION?
Caudal agenesis (sirenomelia)
Premature regression of the primitive streak leads to widespread loss of trunk
and lower limb mesoderm.
VATeR
association:
Vertebral defects
Anal atresia
Tracheo-
esophageal fistula
Renal defects
VACTeRL association:
those above plus…
Cardiovascular
defects
Limb (upper) defects
WHAT HAPPENS IF THERE IS “TOO MUCH”
GASTRULATION?
Sacrococcygeal teratoma
If the primitive streak fails to regress, multipotent primitive streak cells can develop into
multi-lineage tumors (containing ecto-, meso-, and endodermal tissues).
THE EMBRYONIC
The periodPERIOD
in which each of the three germ layers will
give rise to a number of specific tissues and organs
(week 3-8)
Ectodermal germ layers
Initially the ectodermal germ layer has shape of a disc,
not equal at caudal and cranial points
Notocord and precordal mesoderm induces
overlying ectoderm to thicken and form the
neuro plate
Induction of neuroectoderm is the initiation of
neurulation Process by which neuro tube is formed
from neuro plate
NEURAL CREST CELLS
These are cells at the lateral border of the
neuroectoderm
During fusing of the neuro folds the cells will
undergo the epithelial to mesenchymal
transition
Migrates from neuroectoderm to underlying
mesoderm
Neuro crest cells of the trunk region start
migrating in 2 directions following closure of
the neuro tube
• Dorsal and ventral
• Ectoderm germ layer gives raise to organs and
structures that maintain contact with the
outside world
Mesodermal germ layer
Mesodermal germ layer tissue under goes
proliferation
Midline form a thickened tissue known as
paraxial mesoderm
Laterally remain thin and called lateral
plate
Lateral plate divides into somatic or parietal
mesoderm layer continuous with amnion
The layer continuous with the yolk sac is the
splanchnic or visceral mesoderm layer
Paraxial mesoderm
• Segmental organization known as somitomeres
and form in a cephalocaudal manner
• Somitomeres further organise into somites
• First pair arise from the occipital region at
approximately 20th day of development then they
appear at the rate of 3 pairs per day until week 5
• 32 to 34 pairs are present, 4 occipital, 8 cervical,
12 thoracic, 5 lumber, 5 sacral and 8 to 10
coccygeal pairs
• Age determination
Intermediate mesoderm
• Forms segmental cell clusters, future
nephrotome
• More caudally it forms an unsegmented mass of
tissue, the nephrogenic cord
• Excretory units of the urinary system and gonads
form
Lateral plate mesoderm
• Differentiate into visceral and parietal mesoderm
Endodermal germ layer
The gastrointestinal tract is the main organ
system derived from the endodermal germ layer
the epithelial lining of the respiratory tract
the Parenchyma of the thyroid,
parathyroids, liver, and pancreas
the reticular stroma of the tonsils and thymus
the epithelial lining of the urinary bladder and
urethra
the epithelial lining of the tympanic cavity and
auditory tube
MOLECULAR
EMBRYOLOGY
GENE REGULATION OF
SPECIFIC ORGAN
Development of forebrain and midbrain by
inhibition of BMP4 express OTX1,2, EMX 1,
EMX 2 FGF-8 induce expression to brain
development
Development of hindbrain by expression pf hox
gene
Pharyngeal arch 1st arch by OTX2 gene and 2-6th
arch by HOX gene (upregulate by SHH and
retinoic acid)
Spinal cord induce by WNT3a and FGF
upregulare PAX 3,7 for sensory neuron and SHH
for motor neuron
GENE REGULATION OF
SPECIFIC ORGAN
Cardiac development BMP 2,4 + Inhibitor WNT gene
stimulate NKX 2.5 form endoderm anterior cranial
Gut development by SHH Hox gene induce midgut
and hindgut
Liver development from cardiac mesoderm bloking
inhibitory signal in prospective hepatic region cell
differentiate to hepatocyte and biliacy cell lineage regulate
partiall by HNF 3,4 (Hepatocyte Nucelar Transcription
Factor 3 & 4)
GENE REGULATION OF
SPECIFIC ORGAN
Pancreas development from notochord FGF and activin suppress SHH
upregulate PDX gene ; PAX 4,6 specify endocrine cell lineage
Kidney development FGF-2 stimulate proliferation metanephric cap
maintain production WT-1 regulate GDNF and HGF stimulate growth
urteric bud
Genital development (male) SRY gene upregulate SF 1 SOX-9
stimulate differentiation of Sertoli cell and Leydig cell ; Sertoli cell secrete
MIS (Mullerian inhibiting) inhibit paramesonephric duct development
of Wolfian duct
Genital development (female) DAX 1 gene down regulate SRY gene
estrogen and WNT4 cause paramesonephric (Mullerian) duct develop
GENE REGULATION OF
SPECIFIC ORGAN
Limb development initiated by FGF-10 gen FGF4 and
FGF8 patterning of anteroposterior by SHH and
dorsoventral axis by WNT71 induce expression of LMX1
Both type and shape of extremities regulate by HOX gene
combine with SHH, FGF, and WNT77a
REFEREN
CES
• Langmans’s Medical Embryology, 12th ed
• Phillip M. Ecker et al, An animated tour of
human development, version 1.1.
