title: Development-on-chip: in vitro neural tube patterning with a microfluidic device.
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.
authors.affiliation: 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.
authors.forename: Christopher J
authors.identifier: 0000-0002-1470-1364
authors.initials: CJ
authors.lastname: Demers
authors.affiliation: Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Prabakaran
authors.initials: P
authors.lastname: Soundararajan
authors.affiliation: Microinstruments and Systems Laboratory, University of Maine, Orono, ME 04469, USA.
authors.forename: Phaneendra
authors.initials: P
authors.lastname: Chennampally
authors.affiliation: Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Cox
authors.affiliation: The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
authors.forename: James
authors.identifier: 0000-0002-1020-5240
authors.initials: J
authors.lastname: Briscoe
authors.affiliation: 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 scott.collins@maine.edu.
authors.forename: Scott D
authors.identifier: 0000-0003-0204-5109
authors.initials: SD
authors.lastname: Collins
authors.affiliation: 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.
authors.forename: Rosemary L
authors.identifier: 0000-0001-8483-6777
authors.initials: RL
authors.lastname: Smith
mesh_terms: D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D003198:Computer Simulation; D004867:Equipment Design; D056656:Lab-On-A-Chip Devices; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology; D054259:Neural Tube / Q000196:embryology* / Q000378:metabolism; D013997:Time Factors; D059008:Time-Lapse Imaging; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors
keywords: Differentiation; Microfluidic; Mouse; Neuron; Patterning; Stem cell