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.
Highlights
During spinal cord development, organizing centers surrounding the neural tube, such as the notochord, paraxial mesoderm and roof/ floor plates, release chemical cues directing neural precursor cells to differentiate into mature neurons (Fig. 1)
This article presents two novel microfluidic platforms capable of creating dynamic spatial and temporal microenvironments similar to those found during vertebrate neural development
It should be noted that in our experiments a PM gradient is established, not a sonic hedgehog (SHH) gradient. It has been tacitly assumed throughout this article that activation of the SHH pathways through the agonist PM is equivalent to a SHH gradient
Summary
During spinal cord development, organizing centers surrounding the neural tube, such as the notochord, paraxial mesoderm and roof/ floor plates, release chemical cues directing neural precursor cells to differentiate into mature neurons (Fig. 1). The most studied of these cues is sonic hedgehog (SHH), which is generated in notochord and floor plate cells establishing a ventral (high) to dorsal (low) concentration gradient across the neural tube (Ribes and Briscoe, 2009) directing the differentiation of ventral neural progenitors (Roelink et al, 1995) into highly organized domains of neural subtypes (Bushati and Briscoe, 1994). Received 26 May 2015; Accepted 24 March 2016 molecules are simultaneously released by roof plate cells, concurrently patterning the dorsal half of the neural tube and establishing a cross-repressive boundary between the dorsal and ventral halves of the developing spinal cord (Le Dréau et al, 2012). Current models indicate that these four signaling molecules (SHH, BMP, RA and FGF) jointly coordinate most of the spatial and temporal differentiation of the neural tube (Wilson and Maden, 2005)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
