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.
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.
Linear motifs have an integral role in dynamic cell functions including cell signalling, the cell cycle and others. However, due to their small size, low complexity, degenerate nature, and frequent mutations, identifying novel functional motifs is a challenging task. Viral proteins rely extensively on the molecular mimicry of cellular linear motifs for modifying cell signalling and other processes in ways that favour viral infection. This study aims to discover human linear motifs convergently evolved also in disordered regions of viral proteins, under the hypothesis that these will result in enrichment in functional motif instances. We systematically apply computational motif prediction, combined with implementation of several functional and structural filters to the most recent publicly available human-viral and human-human protein interaction network. By limiting the search space to the sequences of viral proteins, we observed an increase in the sensitivity of motif prediction, as well as improved enrichment in known instances compared to the same analysis using only human protein interactions. We identified > 8,400 motif instances at various confidence levels, 105 of which were supported by all functional and structural filters applied. Overall, we provide a pipeline to improve the identification of functional linear motifs from interactomics datasets and a comprehensive catalogue of putative human motifs that can contribute to our understanding of the human domain-linear motif code and the mechanisms of viral interference with this.
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