Characterization of Guanine Exchange Factors for Rho GTPases in Drosophila

在复杂的多细胞生物体的形成过程中，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，导致转移的形成。这些细胞迁移可以作为单个细胞和一组细胞发生，并且需要引导系统和机制来响应引导线索。Rho家族的小GTP酶通过修饰细胞的内部结构是该机制的关键调节剂。Rho GTP酶就像一个开关，可以通过引导线索来“打开”或“关闭”。一类名为GEF的小GTP酶的调节剂“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的RhoGEFs。为此，我们将利用果蝇中的边界细胞迁移，这是一个强大的模型系统。在那里，我们将研究每一个Rho GEF的作用，我们将通过延时显微镜成像这些GEF消耗的细胞迁移结果。此外，我们将确定它们在细胞群中的位置。总而言之，这种详尽的研究GEF蛋白质将为我们提供重要的信息，集体细胞迁移的调节，这是重要的，我们对这一过程的一般理解。此外，它可能会揭示新的治疗策略。

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.