Institut für Neurobiologie, Universität Münster, D-48149 Münster, Germany.
J Neurosci. 2011 May 11;31(19):7005-15. doi: 10.1523/JNEUROSCI.0459-11.2011.
The development of multicellular organisms requires the well balanced and coordinated migration of many cell types. This is of particular importance within the developing nervous system, where glial cells often move long distances to reach their targets. The majority of glial cells in the peripheral nervous system of the Drosophila embryo is derived from the CNS and migrates along motor axons toward their targets. In the developing Drosophila eye, CNS-derived glial cells move outward toward the nascent photoreceptor cells, but the molecular mechanisms coupling the migration of glial cells with the growth of the eye imaginal disc are mostly unknown. Here, we used an enhancer trap approach to identify the gene spinster, which encodes a multipass transmembrane protein involved in endosome-lysosome trafficking, as being expressed in many glial cells. spinster mutants are characterized by glial overmigration. Genetic experiments demonstrate that Spinster modulates the activity of several signaling cascades. Within the migrating perineurial glial cells, Spinster is required to downregulate Dpp (Decapentaplegic) signaling activity, which ceases migratory abilities. In addition, Spinster affects the growth of the carpet cell, which indirectly modulates glial migration.
多细胞生物的发育需要多种细胞类型的平衡协调迁移。在发育中的神经系统中,这一点尤为重要,其中神经胶质细胞通常需要长距离迁移以到达其靶标。果蝇胚胎周围神经系统中的大多数神经胶质细胞来源于 CNS,并沿着运动轴突向其靶标迁移。在发育中的果蝇眼中,CNS 衍生的神经胶质细胞向外迁移到新形成的感光细胞,但将神经胶质细胞迁移与眼 imaginal disc 生长相耦合的分子机制在很大程度上尚不清楚。在这里,我们使用增强子捕获方法鉴定了基因 spinster,其编码一种参与内体-溶酶体运输的多跨膜蛋白,在许多神经胶质细胞中表达。spinster 突变体的特征是神经胶质细胞过度迁移。遗传实验表明,Spinster 调节几种信号级联的活性。在迁移的周细胞神经胶质细胞中,Spinster 被要求下调 Dpp(Decapentaplegic)信号活性,从而停止迁移能力。此外,Spinster 影响地毯细胞的生长,间接调节神经胶质细胞的迁移。