Cytoskeletal and Cell Cycle Regulation of Cell Migration During Development

项目摘要/摘要 细胞周期调节或形态发生运动的缺陷与许多致病过程有关 被认为是癌症转移的标志。可移动的细胞通常由非自主的 吸引人的和/或令人厌恶的暗示。虽然许多引导各种细胞迁移事件发生的线索 在动物发育过程中，已经确定了整合这些基因的下游分子机制 人们对定向运动的线索知之甚少。在这里，我建议用一种比较的方式来填补这一知识空白 比较了两个远缘类群中的中胚层迁徙前体，蛔虫线虫，C. 线虫和斑马鱼，使用高分辨率亚细胞显微镜，遗传和基因组 接近了。这项拟议的研究将确定上游指导信号如何调节细胞骨架 重排和细胞周期状态，以确保适当的细胞迁移。此前的数据表明，指导意见 细胞的正常迁移需要线索。这项提案的具体目标是：(1)确定 细胞迁移过程中细胞骨架组织和动力学的指导线索以及(2)确定细胞周期如何 调控控制着细胞的迁移。这项工作将揭示识别新的抑制目标的机械信息 细胞迁移和靶向细胞迁移是预防肿瘤转移的关键步骤。

Project Summary/Abstract Defects in cell cycle regulation or morphogenetic movements are associated with many pathogenic processes and are regarded as hallmarks of cancer metastasis. Motile cells are often guided non-autonomously by attractive and/or repulsive cues. While many of the cues that guide the various cell migration events that occur during animal development have been identified the downstream molecular mechanisms that integrate these cues into directed motility are poorly understood. Here, I propose to fill this knowledge gap in a comparative context, comparing mesodermal migratory precursors in two distantly related taxa, the roundworm nematode, C. elegans and the zebrafish, D. rerio, using high-resolution sub-cellular microscopy, genetic and genomic approaches. This proposed research will identify how upstream guidance cues regulate cytoskeletal rearrangements and cell cycle state to ensure proper cell migration. Previous data have shown that guidance cues are required for proper cell migration. The specific aims of this proposal seek to (1) determine the role of guidance cues on cytoskeletal organization and dynamics during cell migration and (2) identify how cell cycle regulation controls cell migration. This work will uncover mechanistic information identifying new targets to inhibit cell migration and therapeutically targeting cell migration is a key step in preventing cancer metastasis.