MECHANISMS OF NUCLEAR MIGRATION IN DEVELOPMENT

细胞迁移事件发生在整个发育过程中，是细胞形成结构和执行特殊功能的分化程序的一部分。确定细胞迁移的分子机制对于更好地理解癌细胞的发展和迁移方式是很重要的。核迁移已被证明是秀丽隐杆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，秀丽隐杆线虫是研究细胞和核迁移的一个很好的模型系统。在秀丽隐杆线虫中，P细胞通常迁移到脊髓背，在那里它们最终产生神经元和外阴。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an -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，更广泛地了解细胞迁移，我们提出了实验来表征这三个基因在核迁移中的作用。Unc-83和ac -1 （unc-84已经克隆）将被克隆，我们大量突变等位基因的病变将被分子表征。然后产生针对这些蛋白质的抗体来确定它们的亚细胞定位。此外，还提出了遗传和分子筛选来确定参与核迁移的其他成分。

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.