Development-on-chip: in vitro neural tube patterning with a microfluidic device

Christopher J Demers; Prabakaran Soundararajan; Phaneendra Chennampally; Gregory A Cox; James Briscoe; Scott D Collins; Rosemary L Smith

doi:10.1242/dev.126847

Development-on-chip: in vitro neural tube patterning with a microfluidic device

Development. 2016 Jun 1;143(11):1884-92. doi: 10.1242/dev.126847.

Authors

Christopher J Demers¹, Prabakaran Soundararajan², Phaneendra Chennampally³, Gregory A Cox⁴, James Briscoe⁵, Scott D Collins⁶, Rosemary L Smith⁷

Affiliations

¹ Microinstruments and Systems Laboratory, University of Maine, Orono, ME 04469, USA Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
² Moffitt Cancer Center, Tampa, FL 33612, USA.
³ Microinstruments and Systems Laboratory, University of Maine, Orono, ME 04469, USA.
⁴ Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA The Jackson Laboratory, Bar Harbor, ME 04609, USA.
⁵ The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
⁶ Microinstruments and Systems Laboratory, University of Maine, Orono, ME 04469, USA Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA [email protected].
⁷ Microinstruments and Systems Laboratory, University of Maine, Orono, ME 04469, USA Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA.

Abstract

Embryogenesis is a highly regulated process in which the precise spatial and temporal release of soluble cues directs differentiation of multipotent stem cells into discrete populations of specialized adult cell types. In the spinal cord, neural progenitor cells are directed to differentiate into adult neurons through the action of mediators released from nearby organizing centers, such as the floor plate and paraxial mesoderm. These signals combine to create spatiotemporal diffusional landscapes that precisely regulate the development of the central nervous system (CNS). Currently, in vivo and ex vivo studies of these signaling factors present some inherent ambiguity. In vitro methods are preferred for their enhanced experimental clarity but often lack the technical sophistication required for biological realism. In this article, we present a versatile microfluidic platform capable of mimicking the spatial and temporal chemical environments found in vivo during neural tube development. Simultaneous opposing and/or orthogonal gradients of developmental morphogens can be maintained, resulting in neural tube patterning analogous to that observed in vivo.

Keywords: Differentiation; Microfluidic; Mouse; Neuron; Patterning; Stem cell.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Body Patterning*
Cell Differentiation
Computer Simulation
Equipment Design
Lab-On-A-Chip Devices*
Mice, Transgenic
Motor Neurons / cytology
Neural Tube / embryology*
Neural Tube / metabolism
Time Factors
Time-Lapse Imaging
Transcription Factors / metabolism

Substances

Transcription Factors