Microfluidic Technologies for Defined Spatio-Temporal Patterning in 3D Neural Tube Organoids

Understanding how cells develop into patterned tissues during early embryonic stages is one of the most essential questions in developmental biology. The neural tube, the early embryonic structure which later becomes the spinal cord, has recently been reconstituted from single mouse embryonic stem cells. This 3D in vitro structure mimics many characteristics of early in vivo morphogenesis, including dorso-ventral patterning. While in-vivo patterning is induced by directional morphogen secretion from the notochord, a separate embryonic structure ventral to the neural tube, in-vitro patterning is, in contrast, induced by a spatially uniform, temporally defined treatment with retinoic acid. To investigate this apparent discrepancy, and to understand the role of directional signalling in neural tube morphogenesis, we propose to develop microfluidic technologies which can define complex in-vitro spatial signalling patterns. We expect that by using such a bioengineered approach, we will, for the first time, impose specific and defined patterning in an in-vitro 3D organoid model, and therefore better understand the relationship between spatio-temporal signalling modulation and morphogenesis.