STEM CELLS AND REGENERATION 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


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 .