Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues

光遗传学控制顶端收缩诱导哺乳动物组织合成形态发生

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作者:Guillermo Martínez-Ara #, Núria Taberner #, Mami Takayama #, Elissavet Sandaltzopoulou, Casandra E Villava, Miquel Bosch-Padrós, Nozomu Takata, Xavier Trepat, Mototsugu Eiraku, Miki Ebisuya

Abstract

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.

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