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轴突导向与损伤——来自Wnt及Wnt信号通路的启示

Axon guidance and injury-lessons from Wnts and Wnt signaling.

作者信息

Onishi Keisuke, Hollis Edmund, Zou Yimin

机构信息

Neurobiology Section Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093, United States.

Neurobiology Section Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093, United States.

出版信息

Curr Opin Neurobiol. 2014 Aug;27:232-40. doi: 10.1016/j.conb.2014.05.005. Epub 2014 Jun 11.

Abstract

Many studies in the past decade have revealed the role and mechanisms of Wnt signaling in axon guidance during development and the reinduction of Wnt signaling in adult central nervous system axons upon traumatic injury, which has profound influences on axon regeneration. With 19 Wnts and 14 known receptors (10 Frizzleds (Fzds), Ryk, Ror1/2 and PTK7), the Wnt family signaling proteins contribute significantly to the wiring specificity of the complex brain and spinal cord circuitry. Subsequent investigation into the signaling mechanisms showed that conserved cell polarity pathways mediate growth cone steering. These cell polarity pathways may unveil general principles of growth cone guidance. The reappeared Wnt signaling system after spinal cord injury limits the regrowth of both descending and ascending motor and sensory axons. Therefore, the knowledge of Wnt signaling mechanisms learned from axon development can be applied to axon repair in adulthood.

摘要

在过去十年中,许多研究揭示了Wnt信号通路在发育过程中轴突导向方面的作用和机制,以及在创伤性损伤后成体中枢神经系统轴突中Wnt信号通路的重新诱导,这对轴突再生具有深远影响。Wnt家族信号蛋白有19种Wnt和14种已知受体(10种卷曲蛋白(Fzds)、Ryk、Ror1/2和PTK7),对复杂的脑和脊髓回路的布线特异性有重要贡献。随后对信号传导机制的研究表明,保守的细胞极性通路介导生长锥转向。这些细胞极性通路可能揭示生长锥导向的一般原理。脊髓损伤后重新出现的Wnt信号系统限制了下行和上行运动及感觉轴突的再生。因此,从轴突发育中学到的Wnt信号传导机制知识可应用于成年期的轴突修复。

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