MECHANISMS OF NUCLEAR MIGRATION IN DEVELOPMENT

细胞迁移事件发生在整个发育过程中，作为分化程序的一部分，允许细胞形成结构并执行专门的功能。重要的是要确定细胞迁移的分子机制，以便更好地了解癌细胞的发育和迁移方式。核迁移已被证明是线虫发育过程中许多细胞迁移事件的一个重要方面。由于其光学清晰度和强大的遗传学，线虫是研究细胞和核迁移的极好的模型系统。在线虫中，P细胞通常迁移到背索，在那里它们最终形成神经元和外阴。两个基因UNC-83或UNC-84的突变通过干扰核迁移来阻止这种迁移，导致成虫不协调和产卵缺陷。此外，UNC-84和第三个基因ANC-1的突变破坏了控制核锚定的机制。为了更全面地了解核迁移的控制和机制，以及更广泛地说，细胞迁移，人们提出了实验来表征这三个基因在核迁移中所起的作用。UNC-83和ANC-1(UNC-84已经克隆)将被克隆，我们大量突变等位基因中的病变将被分子表征。然后，将针对这些蛋白质产生抗体，以确定它们的亚细胞定位。此外，还建议通过基因和分子筛查来确定核迁移所涉及的其他成分。

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.