Remarkable phenotypic plasticity of epithelial cells underlies developmental morphogenesis, epithelial repair and tumor invasiveness. Driving all these behaviors are changes in cell adhesion and the cytoskeleton, and understanding their regulatory pathways in vivo may lead to better diagnosis and treatment of birth defects and cancer. The evolutionarily conserved family of formin proteins have emerged as important cytoskeleton effectors downstream of Rho GTPases. In vitro, they are involved in cytokinesis, cell elongation and migration, and in formation of cell-cell adhesions. However, their function in the context of a whole tissue during morphogenesis has not been explored. The host laboratory established epidermal morphogenesis of the C. elegans embryo as an excellent model for epithelial morphogenesis, in which it is possible to combine powerful genetic and genomic tools with clear imaging of the cytoskeleton at the single cell level. My goal is to find which C. elegans formins play a role in epidermal morphogenesis and elucidate their function in regulating cell-cell adhesion and the cytoskeleton. This will be accomplished through a combination of genetics, 4D microscopy and RNAi. ? ? ?
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