Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues.

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.

Use of viral motif mimicry improves the proteome-wide discovery of human linear motifs.

Linear motifs have an integral role in dynamic cell functions, including cell signaling. However, due to their small size, low complexity, and frequent mutations, identifying novel functional motifs poses a challenge. Viruses rely extensively on the molecular mimicry of cellular linear motifs. In this study, we apply systematic motif prediction combined with functional filters to identify human linear motifs convergently evolved also in viral proteins. We observe an increase in the sensitivity of motif prediction and improved enrichment in known instances. We identify >7,300 non-redundant motif instances at various confidence levels, 99 of which are supported by all functional and structural filters. Overall, we provide a pipeline to improve the identification of functional linear motifs from interactomics datasets and a comprehensive catalog of putative human motifs that can contribute to our understanding of the human domain-linear motif code and the associated mechanisms of viral interference.