Cytoskeletal and Cell Cycle Regulation of Cell Migration During Development

项目总结/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 并且被认为是癌症转移的标志。运动细胞通常被非自主的 吸引和/或排斥的线索。虽然许多引导细胞迁移的线索 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， 对定向运动的线索知之甚少。在这里，我建议以比较的方式填补这一知识空白。 上下文，比较中胚层迁移前体在两个遥远的相关类群，蛔虫线虫，C。 elegans和斑马鱼D. rerio，使用高分辨率亚细胞显微镜，遗传和基因组 方法。这项拟议的研究将确定上游指导线索如何调节细胞骨架 重排和细胞周期状态，以确保适当的细胞迁移。此前的数据显示， 需要适当的细胞迁移的线索。本提案的具体目标是：（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）识别细胞周期如何 调节控制细胞迁移。这项工作将揭示机制信息，确定新的目标，以抑制 细胞迁移和治疗靶向细胞迁移是预防癌症转移的关键步骤。

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.