Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo
Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo
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DOI：
10.1523/jneurosci.5381-06.2007
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发表时间：
2007-06-06
影响因子：
5.3
通讯作者：
Kuner, Rohini
中科院分区：
文献类型：
--
作者：
Deng, Suhua;Hirschberg, Alexandra;Kuner, Rohini
脑信号蛋白和它们的受体，丛蛋白，已经成为重要的细胞信号调节关键的发展过程。B型丛蛋白直接调节各种细胞类型中的肌动蛋白细胞骨架。最近，B型丛蛋白已被证明在关键发育窗口期间在神经系统中以惊人的模式表达。然而，与特征明确的丛蛋白-A家族相反，丛蛋白-B蛋白在脊椎动物体内神经发育和器官发生中的功能作用尚不清楚。在这里，我们已经阐明了两个神经元表达丛蛋白B蛋白，丛蛋白B1或丛蛋白B2，对周围神经系统和中枢神经系统的发展，通过生成和分析组成性基因敲除小鼠的功能贡献。神经系统的发育被发现是正常的小鼠缺乏丛蛋白-B1，而小鼠缺乏丛蛋白-B2表现出缺陷的神经管的关闭和一个显着的混乱的胚胎脑。在分析了绕过神经管缺陷的突变小鼠后，我们观察到在发育中的齿状回、嗅球和小脑中颗粒细胞前体的增殖和迁移中对丛蛋白-B2的关键要求。此外，我们确定了semaphorin 4C作为一个高亲和力的配体丛蛋白-B2的结合和功能测定。脑信号蛋白4C通过丛蛋白B2刺激ErbB-2和RhoA的激活，并增强颗粒细胞前体的增殖和迁移。在缺乏丛蛋白B2的小鼠中，脑信号蛋白4C诱导的心室区成神经细胞增殖被废除。这些遗传和功能分析揭示了在体内脊椎动物神经系统的模式化中对丛蛋白-B2而不是丛蛋白-B1的关键需求。
Semaphorins and their receptors, plexins, have emerged as important cellular cues regulating key developmental processes. B-type plexins directly regulate the actin cytoskeleton in a variety of cell types. Recently, B-type plexins have been shown to be expressed in striking patterns in the nervous system over critical developmental windows. However, in contrast to the well characterized plexin-A family, the functional role of plexin-B proteins in neural development and organogenesis in vertebrates in vivo is not known. Here, we have elucidated the functional contribution of the two neuronally expressed plexin-B proteins, Plexin-B1 or Plexin-B2, toward the development of the peripheral nervous system and the CNS by generating and analyzing constitutive knock-out mice. The development of the nervous system was found to be normal in mice lacking Plexin-B1, whereas mice lacking Plexin-B2 demonstrated defects in closure of the neural tube and a conspicuous disorganization of the embryonic brain. After analyzing mutant mice, which bypassed neural tube defects, we observed a key requirement for Plexin-B2 in proliferation and migration of granule cell precursors in the developing dentate gyrus, olfactory bulb, and cerebellum. Furthermore, we identified semaphorin 4C as a high-affinity ligand for Plexin-B2 in binding and functional assays. Semaphorin 4C stimulated activation of ErbB-2 and RhoA via Plexin-B2 and enhanced proliferation and migration of granule cell precursors. Semaphorin 4C-induced proliferation of ventricular zone neuroblasts was abrogated in mice lacking Plexin-B2. These genetic and functional analyses reveal a key requirement for Plexin-B2, but not Plexin-B1, in patterning of the vertebrate nervous system in vivo.