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• W3146618265 abstract "The ability to mimic and control neuroectoderm (NE) development in vitro has important applications in modeling neurodevelopmental diseases and modulating efficiency and uniformity of brain organoid generation. Current human neural differentiation model-systems can dictate NE cell fate specification but not their morphogenesis. We report a first instance of directing the formation of a structurally reproducible and highly-organized NE tissue from human pluripotent stem cells (hPSCs) that recapitulates architectural and cellular characteristics of early neural tube morphogenesis. These include having a continuous, polarized epithelium and a distinct invagination-like folding, where the NE cells undergo E-to-N-cadherin switching and apical constriction. This is accomplished by spatiotemporal patterning of the mesoendoderm (ME) that guides self-organization of the adjacent NE. We uncover that TGF signaling emanating from endodermal cells is obligatory in NE tissue folding. Notably, evaluation of NE structural dysmorphia, which is uniquely achievable in our model, allows for early detection and quantitative measurement of pathologies mediated by FMR1 silencing in Fragile X Syndrome. Altogether, such unprecedented degree of control over the NE tissue architecture greatly expands the potential applications of human stem cell-modeling for early neural tissue development and pathologies." @default.
• W3146618265 created "2021-04-13" @default.
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• W3146618265 date "2018-01-01" @default.
• W3146618265 modified "2023-09-23" @default.
• W3146618265 title "Spatio-Temporally Patterned Neuroectoderm Tissue Recapitulates Early Neural Tube Morphogenesis and Pathogenesis" @default.
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• W3146618265 doi "https://doi.org/10.2139/ssrn.3231850" @default.
• W3146618265 hasPublicationYear "2018" @default.
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