Cytokinesis is the physical separation of two daughter cells following mitosis or meiosis. Cytokinesis requires a cortical contractile ring that is rich in actin filaments and myosin motor proteins. Constriction of the ring causes formation of a furrow, which progressively narrows the cytoplasmic connection between the daughter cells. Following ring closure, the compacted bridge connecting the two cells is cut during abscission. Thus, cytokinesis is essential for cell division. A cell that fails to accomplish cytokinesis becomes tetraploid and more susceptible to undergo apoptosis. Therefore I hypothesize that a compound specifically targeting cytokinesis machinery would be a good candidate for blocking cell division while avoiding side effects such as the neurotoxicity of microtubule poisons. A century of research on cytokinesis has yielded a wealth of information about its molecular requirements and their high degree of conservation. Cytokinesis is well studied in yeasts, cultured cells and isolated embryos but little is known about how this process happens in a tissue. Here I propose to establish a novel model system to study cytokinesis in an intact epithelium using the nematode C. elegans. First I will characterize the kinetics, geometry and success of division in live cells using time-lapse 3D imaging. I will then use protein depletion, mutant alleles and small molecule inhibitors to test the roles of conserved actomyosin cytoskeletal components and intercellular adhesions in the dynamics of cytokinesis. Thus, the proposed work will define the distinct molecular requirements of cytokinesis that are dictated by the tissue context.