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.

经典的胚胎学研究已成功地应用遗传学和细胞生物学原理来理解胚胎发育。然而，仍未解决力学作为发展的整体驱动力如何参与控制组织尺度的细胞命运模式的过程。在这里，我们报告一个基于微模式的人类多能干（hPS）细胞为基础的神经外胚层发育模型，其中预先构图的几何限制诱导了神经上皮和神经板边界细胞的出现模式，模仿了体内早期神经形成过程中神经外胚层的区域化。在这种基于hPS细胞的神经外胚层模式模型中，两个组织规模的形态发生信号-细胞形状和细胞骨架收缩力-通过BMP-SMAD信号指示神经上皮/神经板边界模式。我们进一步表明，异位机械激活和外源BMP信号调制足以扰动神经上皮/神经板边界图案。这项研究提供了有用的，基于hPS细胞的微工程模型，通过该模型可以了解指导神经外胚层模式的生物力学原理，从而研究神经发育和疾病。