Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo. In this hPS-cell-based neuroectoderm patterning model, two tissue-scale morphogenetic signals—cell shape and cytoskeletal contractile force—instruct neuroepithelial/neural plate border patterning via BMP-SMAD signalling. We further show that ectopic mechanical activation and exogenous BMP signalling modulation are sufficient to perturb neuroepithelial/neural plate border patterning. This study provides a useful microengineered, hPS-cell-based model with which to understand the biomechanical principles that guide neuroectoderm patterning and hence to study neural development and disease.
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We thank A. Liu for comments on the manuscript. This work is supported in part by the National Science Foundation (CMMI 1129611 and CBET 1149401 to J.F. and CMMI 1662835 to Y. Sun), the American Heart Association (12SDG12180025 to J.F.) and the Department of Mechanical Engineering at the University of Michigan. The Lurie Nanofabrication Facility at the University of Michigan, a member of the National Nanotechnology Infrastructure Network funded by the National Science Foundation, is acknowledged for support in microfabrication.
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Nature Materials (2018)