Sepp Katharine J, Auld Vanessa J
Department of Zoology, University of British Columbia, Vancouver, Canada V6T 1Z4.
J Neurosci. 2003 Sep 10;23(23):8221-30. doi: 10.1523/JNEUROSCI.23-23-08221.2003.
A major developmental role of peripheral glia is to mediate sensory axon guidance; however, it is not known whether sensory neurons influence peripheral glial development. To determine whether glia and neurons reciprocally interact during embryonic development, we ablated each cell type by overexpressing the apoptosis gene, grim, and observed the effects on peripheral nervous system (PNS) development. When neurons are ablated, glial defects occur as a secondary effect, and vice versa. Therefore glia and neurons are codependent during embryogenesis. To further explore glial-neuronal interactions, we genetically disrupted glial migration or differentiation and observed the secondary effects on sensory neuron development. Glial migration and ensheathment of PNS axons was blocked by overexpression of activated Rho GTPase, a regulator of actin dynamics. Here, sensory axons extended to the CNS without exhibiting gross pathfinding errors. In contrast, disrupting differentiation by expression of dominant-negative Ras GTPase in glia resulted in major sensory axon pathfinding errors, similar to those seen in glial ablations. Glial overexpression of transgenic components of the epidermal growth factor receptor (EGFR) signaling pathway yielded similar sensory neuron defects and also downregulated the expression of the glial marker Neuroglian. Mutant analysis also suggested that the EGFR ligands Spitz and Vein play roles in peripheral glial development. The observations support a model in which glia express genes necessary for sensory neuron development, and these genes are potentially under the control of the EGFR/Ras signaling pathway.
外周神经胶质细胞的一个主要发育作用是介导感觉轴突导向；然而，感觉神经元是否影响外周神经胶质细胞的发育尚不清楚。为了确定胶质细胞和神经元在胚胎发育过程中是否相互作用，我们通过过表达凋亡基因grim来消融每种细胞类型，并观察其对外周神经系统（PNS）发育的影响。当神经元被消融时，胶质细胞缺陷作为次要效应出现，反之亦然。因此，在胚胎发生过程中，胶质细胞和神经元相互依赖。为了进一步探索胶质细胞与神经元之间的相互作用，我们通过基因手段破坏胶质细胞的迁移或分化，并观察其对感觉神经元发育的次要影响。通过过表达激活的Rho GTPase（一种肌动蛋白动力学调节剂）来阻断PNS轴突的胶质细胞迁移和包裹。在此，感觉轴突延伸至中枢神经系统，未表现出明显的路径寻找错误。相反，通过在胶质细胞中表达显性负性Ras GTPase来破坏分化，导致主要的感觉轴突路径寻找错误，类似于在胶质细胞消融中所见。胶质细胞中表皮生长因子受体（EGFR）信号通路转基因成分的过表达产生了类似的感觉神经元缺陷，并且还下调了胶质细胞标志物Neuroglian的表达。突变分析还表明，EGFR配体Spitz和Vein在外周神经胶质细胞发育中起作用。这些观察结果支持了一个模型，即胶质细胞表达感觉神经元发育所需的基因，并且这些基因可能受EGFR/Ras信号通路的控制。
