Radial Glial Cell–Neuron Interaction Directs Axon Formation at the Opposite Side of the Neuron from the Contact Site
Radial Glial Cell–Neuron Interaction Directs Axon Formation at the Opposite Side of the Neuron from the Contact Site
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DOI：
10.1523/jneurosci.1266-15.2015
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发表时间：
2015-10
期刊：
影响因子：
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通讯作者：
Chundi Xu;Yasuhiro Funahashi;Takashi Watanabe;Tetsuya Takano;Shinichi Nakamuta;T. Namba;K. Kaibuchi
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文献类型：
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作者：
Chundi Xu;Yasuhiro Funahashi;Takashi Watanabe;Tetsuya Takano;Shinichi Nakamuta;T. Namba;K. Kaibuchi
细胞外信号如何影响小鼠发育神经元的直接轴突-树突极化尚不完全清楚。在这里，我们报告放射状胶质细胞（RGC）与皮质神经元的相互作用指导神经元与接触部位相反一侧的轴突形成。 N-钙粘蛋白在 RGC 和皮质神经元之间的接触部位积聚。抑制 N-钙粘蛋白介导的粘附会减少体外定向轴突的形成，并破坏体内轴突-树突的极化。此外，RGC-神经元相互作用诱导接触神经突处活性 RhoA 和相对神经突处活性 Rac1 的极化分布。抑制神经元中的 Rho-Rho-激酶信号传导会损害体外定向轴突形成，并防止体内轴突-树突极化。总的来说，这些结果表明，N-钙粘蛋白介导的放射状胶质细胞-神经元相互作用决定了接触神经突作为放射状胶质细胞引导神经元迁移的主导过程，并通过 Rho 家族 GTP 酶将轴突形成引导到对侧。意义声明神经元是高度极化的细胞系，通常具有单个轴突和多个树突，这是大脑中整合和传输信息的能力的基础。发育中的新皮质中神经元的轴突-树突极性是如何建立的？在这里，我们表明，N-钙粘蛋白介导的放射状胶质细胞-神经元相互作用指导轴突-树突极化，放射状胶质细胞-神经元相互作用诱导神经元中活性RhoA和活性Rac1的极化分布，而轴突-树突极化需要Rho-Rho激酶信号传导。我们的工作增进了对细胞外信号如何在小鼠发育神经元中直接轴突-树突极化的整体理解。
How extracellular cues direct axon–dendrite polarization in mouse developing neurons is not fully understood. Here, we report that the radial glial cell (RGC)–cortical neuron interaction directs axon formation at the opposite side of the neuron from the contact site. N-cadherin accumulates at the contact site between the RGC and cortical neuron. Inhibition of the N-cadherin-mediated adhesion decreases this oriented axon formation in vitro, and disrupts the axon–dendrite polarization in vivo. Furthermore, the RGC–neuron interaction induces the polarized distribution of active RhoA at the contacting neurite and active Rac1 at the opposite neurite. Inhibition of Rho–Rho-kinase signaling in a neuron impairs the oriented axon formation in vitro, and prevents axon–dendrite polarization in vivo. Collectively, these results suggest that the N-cadherin-mediated radial glia–neuron interaction determines the contacting neurite as the leading process for radial glia-guided neuronal migration and directs axon formation to the opposite side acting through the Rho family GTPases. SIGNIFICANCE STATEMENT Neurons are highly polarized cell lines typically with a single axon and multiple dendrites, which underlies the ability of integrating and transmitting the information in the brain. How is the axon–dendrite polarity of neurons established in the developing neocortex? Here we show that the N-cadherin-mediated radial glial cell–neuron interaction directs axon–dendrite polarization, the radial glial cell–neuron interaction induces polarized distribution of active RhoA and active Rac1 in neurons, and Rho–Rho-kinase signaling is required for axon–dendrite polarization. Our work advances the overall understanding of how extracellular cues direct axon–dendrite polarization in mouse developing neurons.