Optogenetic Control of Apical Constriction Induces 3D Deformation in Mammalian Epithelia

During development, cellular forces come together in a synchronized manner to robustly generate functional tissue shape. Apical constriction is one of these force generating processes, and has been demonstrated to be necessary for the induction of epithelial curvature in fundamental morphogenetic events, such as neural tube folding¹. The emerging field of synthetic developmental biology proposes the use of bottom-up approaches to learn how such processes combine to create functional tissues². However, to this date there’s no tool available to manipulate 3D shape of mammalian tissues. Here we report the development of “OptoShroom3”, a new optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. We demonstrate that OptoShroom3 induced apical constriction can provoke tissue curvature and folding on an MDCK cell sheet. Moreover, its application in eye-cup organoids lead to epithelial thickening and apical lumen reduction in optic vesicles. These results show that spatiotemporal control of apical constriction can be used to generate controlled 3D tissue shape changes in mammalian epithelia. OptoShroom3 also points out the potential of optogentics to gain control over morphogenetic processes and develop tissue architectures in vitro.

1. Haigo, S. L., Hildebrand, J. D., Harland, R. M., & Wallingford, J. B. (2003). Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Current biology, 13(24), 2125-2137.

2.Ebrahimkhani, M. R., & Ebisuya, M. (2019). Synthetic developmental biology: build and control multicellular systems. Current Opinion in Chemical Biology, 52, 9-15.