Characterization of Guanine Exchange Factors for Rho GTPases in Drosophila

在一个复杂的多细胞有机体的形成过程中，一些细胞通过组织迁移到一个精确的地方。在一些癌症中也会发生细胞迁移，导致转移的形成。这些细胞迁移可以作为单个细胞发生，也可以作为一组细胞发生，需要引导系统和机械来对引导提示做出反应。Rho家族的小GTP酶通过改变细胞的内部结构是这一机制的关键调节因子。Rho GTP酶就像开关一样，可以通过引导信号“开启”或“关闭”。一类名为GEF的小分子GTP酶调控因子正在“启动”Rho GTP酶。在这个项目中，我们想要在一个集体细胞迁移的活体模型中表征所有的RhoGEF。为此，我们将利用果蝇的边缘细胞迁移，这是一个强大的模型系统。在那里，我们将研究每一个Rho全球环境基金的作用，我们将通过时间推移显微镜成像这些GEF枯竭对细胞迁移的结果。此外，我们将确定它们在细胞组中的位置。总之，对全球环境基金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，这对于我们对这一过程的总体理解非常重要。此外，它可能会揭开新的治疗策略的面纱。

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.