Grant: Project Grant

Cytokinesis is a critical step of cell division that separates a dividing cell into two daughter cells. In the animal body, cytokinesis does not only contribute to the multiplication of cells, but also to their arrangement within their space, by controlling the position and orientation of division (symmetry-breaking). Although defects in cell division orientation are also associated with cancer cells, the mechanisms underlying the symmetry-breaking of cytokinesis are not well studied. Emerging evidence suggests that cell surface flow of motor protein myosin-cortical flow-is a driving force of spatial control of cytokinesis. The direction of cortical flow is distinct among cell types, but how cortical flow is navigated in three-dimensional space remains largely unknown. Our goal is to elucidate the cortical flow navigation system that breaks symmetry of cytokinesis. Actin cytoskeleton and myosin motor protein are central players of cortical flow generation; thus, we will analyze and identify the molecules and mechanism that regulate them. For our experiments we will use the embryos of a powerful model organism, a roundworm called Caenorhabditis elegans that shares many molecular components involved in cell division and actin-myosin regulation with humans. We will capture the myosin dynamics in the living cells using state-of-the-art microscopy in different cell types and genetic backgrounds. By observing cortical flow control in multiple modes of spatially controlled cytokinesis, we will understand the molecular mechanisms that enable cortical flow navigation during embryogenesis. Our analysis of this fundamental cell division event in the context of animal development will expand the frontiers of cell division research and will provide a basis for curing cancers caused by abnormalities in cytokinesis.