Characterization of Guanine Exchange Factors for Rho GTPases in Drosophila

在复杂的多细胞生物形成过程中，一些细胞通过组织迁移到一个精确的位置。细胞迁移也发生在一些癌症中，引起转移的形成。这些细胞迁移可以以单个细胞或细胞群的形式发生，需要一个引导系统和对引导信号作出反应的机制。Rho家族的小gtpase通过改变细胞的内部结构是这一机制的关键调节器。Rho gtp酶就像通过引导线索“打开”或“关闭”的开关。一类被称为gef的小gtp酶的调节因子正在“开启”Rho gtp酶。在这个项目中，我们希望在集体细胞迁移的体内模型中表征所有rhogef。为此，我们将利用果蝇这一强大的模型系统中的边界细胞迁移。在那里，我们将研究每一个Rho GEF的作用，我们将通过延时显微镜成像这些GEF耗尽后细胞迁移的结果。此外，我们将确定它们在细胞群中的位置。总之，这项对GEF蛋白的详尽研究将为我们提供关于集体细胞迁移调控的重要信息，这对我们对这一过程的总体理解很重要。此外，它可能揭示新的治疗策略。

During the formation of a complex pluricellular organism, some cells migrate through tissues to home at a precise place. Cell migration also occurs in some cancers, causing the formation of metastasis. These cell migrations can occur as single cells and as a group of cells and require a guidance system and the machinery to response to guidance cues. Small GTPases of the Rho family are key regulators of this machinery by modifying the internal structure of the cell. Rho GTPases are like switches that are turned "on" or "off" by guidance cues. A class of regulators of small GTPases named GEFs are "switching on" the Rho GTPases. In this project, we want to characterize all the RhoGEFs in a in vivo model of collective cell migration. For this, we will take advantage of border cell migration in Drosophila, a powerful model system. In there, we will study the role of every single Rho GEF and we will image by time-lapse microscopy the outcome on cell migration of the depletion of these GEFs. Furthermore, we will determine where they localize in the group of cell. Altogether, this exhaustive study of GEF proteins will provide us with important information on the regulation of collective cell migration which is important for our general understanding of this process. In addition, it might unravel new therapeutic strategies.