The emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution of each cellular process to complex morphogenesis. However, the shortage of tools to manipulate three-dimensional (3D) shapes of mammalian tissues hinders the progress of the field. Here we report the development of OptoShroom3, an optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. Activation of OptoShroom3 through illumination in an epithelial Madin-Darby Canine Kidney (MDCK) cell sheet reduces the apical surface of the stimulated cells and causes displacements in the adjacent regions. Light-induced apical constriction provokes the folding of epithelial cell colonies on soft gels. Its application to murine and human neural organoids leads to thickening of neuroepithelia, apical lumen reduction in optic vesicles, and flattening in neuroectodermal tissues. These results show that spatiotemporal control of apical constriction can trigger several types of 3D deformation depending on the initial tissue context.

合成发育生物学的新兴领域提出了自下而上的方法来检查每个细胞过程对复杂形态发生的贡献。然而，操纵哺乳动物组织三维（3D）形状的工具的缺乏阻碍了该领域的进步。在这里，我们报告 OptoShroom3 的开发，这是一种光遗传学工具，可实现哺乳动物上皮细胞顶端收缩的快速时空控制。通过光照上皮 Madin-Darby 犬肾 (MDCK) 细胞片激活 OptoShroom3，可减少受刺激细胞的顶端表面并导致邻近区域发生位移。光诱导的顶端收缩引起软凝胶上上皮细胞集落的折叠。其在小鼠和人类神经类器官中的应用导致神经上皮增厚、视神经泡顶腔减少以及神经外胚层组织变平。这些结果表明，根尖收缩的时空控制可以根据初始组织环境触发多种类型的 3D 变形。