Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues

Abstract

During embryonic development, cellular forces synchronize in space and time to generate functional tissue shapes. Apical constriction is one of these force-generating processes, and it is necessary to modulate epithelial curvature in fundamental morphogenetic events, such as neural tube folding. 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 currently hinders the progress of the field. Here we report the development of 'OptoShroom3', a new optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. Activation of OptoShroom3 through illumination of individual cells in an epithelial cell sheet reduced their apical surface while illumination of groups of cells caused deformation in the adjacent regions. By using OptoShroom3, we further manipulated 3D tissue shapes. Light-induced apical constriction provoked the folding of epithelial cell colonies on soft gels. Its application to murine and human neural organoids led 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.

Optogenetic relaxation of actomyosin contractility uncovers mechanistic roles of cortical tension during cytokinesis

“…The OptoMYPT system will provide opportunities not only to understand the mechanics of morphogenesis, but also to shape the morphology of cells and tissues with precision and flexibility as desired. Recent papers have applied optogenetic systems in vivo, and succeeded in inducing arbitrary forms of apical constriction 61,62 . By combining red light-responsive optogenetic tools such as PhyB-PIF with blue light-responsive tools 63,64 , it will be possible to create more sophisticated morphology with an increase or decrease in contractile force in the same cells and tissues.…”

Engineering Brain Organoids: Toward Mature Neural Circuitry with an Intact Cytoarchitecture

“…In a study, the light activable Wnt system was used to drive mesoderm-specific differentiation of hPSCs along with the induction of subpopulation-wise self-organization of cells in a 3D culture ( 45 ). Similarly, optical control of curvature in neuroectodermal organoids was reported, indicating the possibility to modulate brain organoid morphogenesis using a light-activable system ( 46 ). A more recent study has utilized a light-inducible Cre/Lox recombination system to activate the expression of SHH only in the photo-stimulated area within the neural organoid, resulting in the establishment of the dorsoventral positional identity ( 47 ).…”

Retina organoids: Window into the biophysics of neuronal systems

“…have developed an optogenetic method to reversibly control the active myosin concentration by triggering a light-sensitive molecular switch for apical myosin activation (Optoshroom3). 133 Importantly, the optical activation of cellular forces has allowed to reversibly change tissue shape. This permits to isolate the role of mechanical forces for shape formation of the organoid.…”