MECHANISMS OF NUCLEAR MIGRATION IN DEVELOPMENT

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Cell migration events occur throughout development as a part of a differentiation program to allow cells to form structures and perform specialized functions. It is important to determine the molecular mechanisms of cell migration to better understand both development and how a cancer cell migrates. Nuclear migration has been shown to be an important aspect of many cellular migration events during C elegans development. Because of its optical clarity and powerful genetics, C. elegans is an excellent model system in which to study cellular and nuclear migrations. In C. elegans, the P cells normally migrate to the dorsal cord where they eventually give rise to neurons and the vulva. Mutations in two genes, unc-83 or unc-84, block this migration by interfering with nuclear migration, leading to an adult worm that is uncoordinated and egg-laying defective. In addition, mutations in unc-84 and a third gene, anc-1, disrupt mechanisms controlling nuclear anchorage. In order to more fully understand the control and mechanisms of nuclear migration, and more generally, cellular migrations, experiments are proposed to characterize the roles these three genes play in nuclear migration. unc-83 and anc-1 (unc-84 is already cloned) will be cloned, and the lesions in our large collection of mutant alleles will be molecularly characterized. Then antibodies will be raised against these proteins to determine their sub-cellular localization. Additionally, genetic and molecular screens are proposed to identify other components involved in nuclear migration.