Department of Biology, Northeastern University, 360 Huntington Ave, 134 Mugar Hall, Boston, MA 02115, USA.
Dev Biol. 2010 May 1;341(1):176-85. doi: 10.1016/j.ydbio.2010.02.025. Epub 2010 Feb 25.
The two specialized C. elegans distal tip cells (DTCs) provide an in vivo model system for the study of developmentally regulated cell migration. We identified cacn-1/cactin, a well-conserved, novel regulator of cell migration in a genome-wide RNAi screen for regulators of DTC migration. RNAi depletion experiments and analysis of the hypomorphic allele cacn-1(tm3126) indicate that CACN-1 is required during DTC migration for proper pathfinding and for cessation of DTC migration at the end of larval morphogenesis. Strong expression of CACN-1 in the DTCs, and data from cell-specific RNAi depletion experiments, suggest that CACN-1 is required cell-autonomously to control DTC migration. Importantly, genetic interaction data with Rac GTPase activators and effectors suggest that CACN-1 acts specifically to inhibit the mig-2/Rac pathway, and in parallel to ced-10/Rac, to control DTC pathfinding.
两个特化的秀丽隐杆线虫远端 tip 细胞(DTC)为研究发育调控的细胞迁移提供了一个体内模型系统。我们在一个针对 DTC 迁移调控因子的全基因组 RNAi 筛选中,发现了 cacn-1/cactin,这是一种在进化上保守的、新型的迁移调控因子。RNAi 耗竭实验和 cacn-1(tm3126) 次等位基因的分析表明,CACN-1 在 DTC 迁移过程中对于正确的路径选择和幼虫形态发生结束时 DTC 迁移的停止是必需的。CACN-1 在 DTC 中的强表达,以及来自细胞特异性 RNAi 耗竭实验的数据,表明 CACN-1 是自主控制 DTC 迁移所必需的。重要的是,与 Rac GTPase 激活剂和效应器的遗传相互作用数据表明,CACN-1 特异性地抑制 mig-2/Rac 途径,与 ced-10/Rac 平行,以控制 DTC 的路径选择。