Mechanics-guided Embryonic Patterning of Neuroectoderm Tissue from Human Pluripotent Stem Cells

Overview

Journal Nat Mater

Date 2018 May 23

PMID 29784997

Citations 83

Authors

Xufeng Xue

Yubing Sun

Agnes M Resto-Irizarry

Ye Yuan

Koh Meng Aw Yong

Yi Zheng

Shinuo Weng

Yue Shao

Yimin Chai

Lorenz Studer

Jianping Fu

Affiliations

Soon will be listed here.

Abstract

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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