Regulation of Cytoskeletal Dynamics

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My research program studies the intracellular control of cytokinesis, which separates mother cells into daughters during mitosis, and intercellular control of collective cell movements for tissue morphogenesis. These research themes are tied by our interest in the regulation of cytoskeletal dynamics, and actomyosin filaments in particular. For cytokinesis, we study mechanisms that precisely control the actomyosin ring that pinches in the cytosol and membrane of cells. The ring must be spatiotemporally controlled to ensure that the chromosomes and cell fate determinants are properly inherited into each daughter cell. Prior studies showed that the mitotic spindle provides cues to regulate actomyosin ring formation, and several models were derived to explain how this could work in different cell types and organisms. However, the majority of these studies were done on single cells in model organisms, or using cancer cells grown in a dish. We uncovered another pathway that functions via chromatin to regulate cytokinesis in parallel with the mitotic spindle. This pathway may help us to understand how cytokinesis is uniquely regulated in different cells, and we will study this pathway in cells that are important for development; with different polarity, altered ploidy or different size. For tissue morphogenesis, we study mechanisms that coordinate actomyosin regulation of cell shape changes and migration. The failure to coordinate cells can prevent tissues from developing properly. However, few studies have followed tissue morphogenesis in vivo, and it is not clear how intercellular signaling coordinates cells within or between tissues. Further, most studies of morphogenesis were done using isolated epidermal tissue, and the development of other tissues is less-well understood. We use C. elegans as a model organism due to their simple body plan, amenability to microscopy and their establishment as a genetic model. We found that during C. elegans epidermal morphogenesis, a subset of neuroblasts (neuronal precursor cells) undergo morphogenesis concomitant with the overlying epidermis. The neuroblasts shrink in surface area and undergo organizational changes, and we found that altering myosin contractility selectively in these cells disrupts migration of the overlying epidermal cells. Therefore, we are well-positioned to further characterize neuroblast morphogenesis, a non-epidermal tissue that is crucial for metazoans. Also, we will determine how mechanical forces coordinate neuroblast and epidermal morphogenesis.