![]() ![]() In this study, we present an optogenetic tool that achieves control of apical constriction in mammalian cells, inducing multiple types of 3D tissue deformation. ![]() However, the manipulation of organoid shape with optogenetic tools remains unexplored. ![]() In addition, the recent development of organoids, stem cell-derived 3D structures 23, 24, 25, offers unique opportunities to study the interplay between tissue shape and function in vitro. Therefore, there is still a lack of tools to manipulate 3D tissue deformation and reconstitute mammalian morphogenesis. Since all previous tools have been based on recruitment to the plasma membrane, they require a precise multi-photon stimulation of the apical membrane to induce constriction of the apical side only. However, this approach has been mainly applied to study cell-level events, and its application to induce morphogenesis in complex tissue shapes is technically challenging. The approach has been effectively used to study mechanotransduction 19, cell junction remodeling 20, cytoskeletal dynamics 21, and cytokinesis 22. Similar tools have been developed to spatiotemporally increase or reduce contractility in mammalian cells, mainly through recruiting RhoGEF, RhoA, or myosin regulators to the plasma membrane. Selective optogenetic activation on the apical side of dorsal cells led to tissue invagination, demonstrating that apical constriction is sufficient to induce deformation in that context 18. employed optogenetics to recruit RhoGEF to the plasma membrane in Drosophila embryos. Optogenetics is a powerful methodology to gain spatiotemporal control of biological processes from the molecular to the multicellular level 9, 10, 11, 12, 13, 14, 15, 16, 17. Because apical constriction occurs in specific stages and areas of the developing embryo, reconstituting curved tissues requires tools to control cellular contractility in space and time. The driving force of apical constriction is actomyosin contraction, which is often triggered by activation of the Rho-ROCK pathway on the apical side. As a solution, the field of synthetic morphology 1 or synthetic developmental biology 2, 3, 4, 5, 6 proposes to reconstitute morphogenetic events in vitro by gaining control of the constituent cell-level mechanisms.Īpical constriction, a process by which a cell actively reduces its apical surface, is necessary for the formation of numerous curved structures in metazoan embryos 7, 8. However, it is difficult to test the sufficiency of a mechanism to cause a specific change in tissue structure and to study feedback between multiple mechanisms during complex embryogenesis. The study of developing embryos has identified cell-level mechanisms that need to be coordinated to achieve morphogenesis. Morphogenesis is the process by which cells organize to form 3D tissues and organs. These results show that spatiotemporal control of apical constriction can trigger several types of 3D deformation depending on the initial tissue context. Its application to murine and human neural organoids leads to thickening of neuroepithelia, apical lumen reduction in optic vesicles, and flattening in neuroectodermal tissues. Light-induced apical constriction provokes the folding of epithelial cell colonies on soft gels. ![]() 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. Here we report the development of OptoShroom3, an optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. However, the shortage of tools to manipulate three-dimensional (3D) shapes of mammalian tissues hinders the progress of the field. The emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution of each cellular process to complex morphogenesis. ![]()
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