FGF receptor dependent cell migration in Drosophila

果蝇中胚层和气管分支网络的形成与细胞迁移、细胞形态改变和细胞重排有关。这两种组织的形态发生都受FGF信号转导途径的控制。该项目旨在确定FGF信号通路的组成部分引起运动行为的机制。第一步将是研究FGF信号转导通路激活后中胚层细胞和气管细胞内发生的变化。最初，一些标记将用于获得细胞骨架的详细描述，极性和参与野生型胚胎这些形态发生过程的细胞的亚细胞事件。此外，将使用电子显微镜研究中胚层向外胚层扩散时所形成的特定细胞接触。然后，我们将研究当FGF信号转导通路被破坏时，这些事件是如何受到影响的，以及这些影响是如何根据发生破坏的信号通路的水平而不同的。在Dof突变胚胎中观察到的FGF靶基因的形态发生和激活缺陷，通过检测Dof突变蛋白的突变形式在多大程度上可以挽救FGF靶基因的激活，来研究Dof的作用。希望这一策略能够识别与不同功能相关的蛋白质部分，特别是与细胞骨架连接所必需的部分，并阐明FGF信号转导途径影响细胞迁移的机制。

The formation of the mesoderm and the branched network of the tracheae in Drosophila is associated with cell migration, changes in cell shape and cell rearrangements. The morphogenesis of both of these tissues is controlled by the FGF signal transduction pathway. This project aims to identify the mechanism by which the components of the FGF signalling pathway cause motile behaviour. The first step will be to investigate the changes that occur within mesodermal and tracheal cells upon activation of the FGF signal transduction pathway. Initially a number of markers will be used to gain a detailed description of the cytoskeleton, the polarity and the subcellular events of the cells that take part in these morphogenetic processes in wildtype embryos. In addition, the specific cell contacts made by the mesoderm as it spreads out on the ectoderm will be investigated using electron microscopy. We will then study how these events are affected when the FGF signal transduction pathway is disrupted, and how the effects differ depending on the level of the signalling pathway at which the disruption occurs. The role of Dof in particular will be investigated by examining the extent to which mutant forms of the protein can rescue the defects in morphogenesis and activation of FGF target genes that are observed in Dof mutant embryos. It is hoped that this strategy will identify parts of the protein associated with distinct functions, especially those necessary for the link to the cytoskeleton, and shed light on the mechanisms by which the FGF signal transduction pathway affects cell migration.