Spatio-temporally patterned neuroectoderm tissues recapitulate early neural morphogenesis and pathogenesis

Current human neural differentiation model-systems can dictate neuroectoderm (NE) cell fate specification but not their morphogenesis. We report a first instance of directing the formation of a human-specific NE tissue that recapitulates architectural and cellular characteristics of early neural tube morphogenesis, including, a continuous, polarized epithelium and a distinct invagination-like folding, where the NE cells undergo apical constriction. This is accomplished by spatiotemporal patterning of the mesoendoderm that guides self-organization of the adjacent NE. Notably, evaluation of NE structural dysmorphia, which is uniquely achievable in our model, allowed for early detection of pathologies mediated by FMR1 silencing in Fragile X Syndrome.