Cytokinesis and RNA Segregation in Zebrafish Development

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Cytokinesis, the physical process that divides daughter cells, is of fundamental importance to development and growth regulation. In many instances, cytokinesis is coupled with the asymmetric segregation of cellular determinants, which in turn results in the functional diversification of cell types. A basic question in biology is to understand the molecular mechanisms underlying the segregation of cell fate determinants, in particular the germ plasm, a specialized cytoplasm that confers the germ cell fate. Systematic screens for maternal-effect mutations in the zebrafish, Danio rerio, have identified genes that affect the processes of cytokinesis and germ plasm segregation, which in this organism are intimately linked. The gene aura appears to be involved in membrane and/or f-actin dynamics required for cell division and germ plasm recruitment, cellular island, which likely codes for the chromosomal passenger protein aurora B kinase, is involved in furrow initiation. The gene nebel, which likely encodes L-aspartate dehydrogenase is important for the amplification of calcium waves associated with furrow maturation and germ plasm compaction. In addition, we have identified a role for non-muscle myosin II in furrow maturation and germ plasm segregation. The proposed research will determine the precise roles of these genes and other subcellular events, such as cytoskeletal rearrangements, cortical transport and membrane exocytosis, within the coordinated pathway of events that drives cytokinesis and germ plasm segregation. The understanding of these processes will provide insights on a variety of poorly understood subjects: i) the events involved in cytokinesis, ii) the asymmetric segregation of germ plasm components within dividing cells, and iii) the functional relationship between the cellular mechanisms required for these two processes.