Axon regeneration is limited in the central nervous system, which hinders the reconstruction of functional circuits following spinal cord injury (SCI). Although various extrinsic molecules to repel axons following SCI have been identified, the role of semaphorins, a major class of axon guidance molecules, has not been thoroughly explored. Here we show that expression of semaphorins, including Sema5a and Sema6d, is elevated after SCI, and genetic deletion of either molecule or their receptors (neuropilin1 and plexinA1, respectively) suppresses axon retraction or dieback in injured corticospinal neurons. We further show that Olig2⁺ cells are essential for SCI-induced semaphorin expression, and that Olig2 binds to putative enhancer regions of the semaphorin genes. Finally, conditional deletion of Olig2 in the spinal cord reduces the expression of semaphorins, alleviating the axon retraction. These results demonstrate that semaphorins function as axon repellents following SCI, and reveal a novel transcriptional mechanism for controlling semaphorin levels around injured neurons to create zones hostile to axon regrowth.

中文翻译：

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Olig2 诱导的信号素表达在脊髓损伤后驱动皮质脊髓轴突回缩。

轴突再生在中枢神经系统中受到限制，这阻碍了脊髓损伤 (SCI) 后功能回路的重建。尽管已经确定了各种外在分子来排斥 SCI 后的轴突，但信号素（一类主要的轴突引导分子）的作用尚未得到彻底探索。这里，我们显示的表达脑信号蛋白S，其中包括SEMA5A和Sema6d中，脊髓损伤后升高，并且基因缺失或者分子或它们的受体的（neuropilin1和plexinA1，分别地）禁止显示轴突回缩或受伤的神经元皮质顶梢枯死。我们进一步表明 Olig2 ⁺细胞对于 SCI 诱导的信号素表达至关重要，并且 Olig2 与信号素基因的推定增强子区域结合。最后，有条件地删除脊髓中的Olig2会降低信号素的表达，从而减轻轴突回缩。这些结果表明，semaphorins 在 SCI 后起到轴突驱避剂的作用，并揭示了一种新的转录机制，用于控制受损神经元周围的 semaphorin 水平，以创建对轴突再生不利的区域。