Glial cell migration in Drosophila

在许多后生动物中发现的定型轴突网络的形成依赖于神经元和胶质细胞的复杂相互作用，并且需要任何一种细胞类型的迁移。在果蝇中枢神经系统中，中线胶质细胞的迁移是建立节段性连接所必需的。这种迁移的阻断导致CNS表型突变，这使我们能够对中线胶质细胞迁移所需的基因进行饱和EMS诱变筛选。在超过13个基因中发现了突变。其中四种影响控制中线胶质细胞分化的EGF受体信号。凯特在中线神经元中起作用，影响轴突的形成，中线胶质细胞沿着轴突迁移。在这里，我有两个不同的相关项目，旨在了解果蝇胚胎神经系统中神经胶质迁移的分子机制。在第一个项目中，我们计划对schmalspur基因进行分子分析，该基因似乎在中线神经胶质中表达。根据表型分析和我们观察到的与神经元表达基因kette的遗传相互作用，schmalspur是一个非常有前途的与胶质细胞迁移相关的候选基因。在第二个项目中，我们希望建立新的基因筛选系统，旨在更直接地解决胶质细胞迁移问题。我们将重点分析胚胎和幼体PNS的周围神经胶质细胞，因为只有在这里可以观察到广泛的迁移。为了确定相关的基因，我们将采用几种技术。我们将使用最近描述的MARCM系统建立经典的F3方法和改进的FRT/FLP方法。最后，我们希望建立一个新的胶质细胞特异性基因沉默系统。

The formation of the stereotyped axonal network found in many metazoan organisms depends on the intricate interplay of neuronal and glial cells and requires migration of either cell type. In the Drosophila CNS, migration of the midline glial cells is required for the establishment of the segmental commissures. A block in this migration leads to a mutant CNS phenotype which allowed us to conduct a saturating EMS mutagenesis screening for genes required for midline glial cell migration. Mutations in more than 13 genes were identified. Four of them affect EGF receptor signalling which controls differentiation of the midline glia. kette was shown to act in the midline neurons where it affects the formation of axons along which the midline glial cells migrate. Here I purpose two different related projects aimed to understand the molecular mechanisms underlying glial migration in the embryonic nervous system of Drosophila. In the first project we are planing a molecular analysis of the gene schmalspur, which appears to be expressed in the midline glia. Based on the phenotypic analysis and on genetic interactions we observed with the neuronally expressed gene kette, schmalspur is a very promising candidate gene relevant for glial migration. In the second project we want to establish new genetic screening systems aimed to more directly address glial cell migration. We will focus on the analysis of peripheral glial cells in the embryonic as well as in the larval PNS, since only here extensive migrations can be observed. In order to identify the relevant genes we will employ several techniques. We will set up a classical F3 approach and a modified FRT/FLP approach using the recently described MARCM system. Finally, we want to establish a new glial cell specific gene silencing system.