Repulsive Wnt signaling inhibits axon regeneration after CNS injury.
Repulsive Wnt signaling inhibits axon regeneration after CNS injury.
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DOI：
10.1523/jneurosci.1939-08.2008
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发表时间：
2008-08-13
期刊：
影响因子：
--
通讯作者：
Zou Y
中科院分区：
文献类型：
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作者：
Liu Y;Wang X;Lu CC;Kerman R;Steward O;Xu XM;Zou Y
在哺乳动物中枢神经系统（CNS）中轴突再生的失败部分是由于存在各种抑制性分子，包括髓鞘相关蛋白和在胶质瘢痕中富集的蛋白聚糖。在这里，我们评估轴突导向分子是否也调节成年损伤后的再生生长。Wnts是一大家族的轴突导向分子，可以沿着发育中的脊髓的长度吸引上行轴突和排斥下行轴突沿着。它们的表达（所有19个Wnts）在正常成人脊髓原位杂交检测不到。然而，其中三种在脊髓损伤后明显地被重新诱导。Wnt1和Wnt5a，编码皮质脊髓下行束（CST）轴突的强效排斥剂，在脊髓灰质单侧半切后被强烈和急性广泛诱导。Ryk，保守的排斥性Wnt受体，也被诱导在病变区域，和Ryk免疫反应被发现在病变的CST轴突。Wnt4，吸引上升的感觉轴突在发展中，急性诱导比Wnt1和Wnt5a更接近病变的区域。注射功能阻断Ryk抗体到背侧双侧半切脊髓中，可以防止CST轴突的回缩或促进其再生，但明显增强了损伤部位周围和以外的CST侧支的发芽。因此，排斥性Wnt信号可能是皮质脊髓束轴突回缩的原因，并抑制损伤后的轴突发芽。
Failure of axon regeneration in the mammalian central nervous system (CNS) is due in part to the presence of various inhibitory molecules, including myelin-associated proteins and proteoglycans enriched in glial scars. Here we evaluate whether axon guidance molecules also regulate regenerative growth after injury in adulthood. Wnts are a large family of axon guidance molecules, which can attract ascending axons and repel descending axons along the length of the developing spinal cord. Their expression (all 19 Wnts) is not detectable in normal adult spinal cord by in situ hybridization. However, three of them are clearly reinduced after spinal cord injury. Wnt1 and Wnt5a, encoding potent repellents of the descending corticospinal tract (CST) axons, were robustly and acutely induced broadly in the spinal cord gray matter following unilateral hemisection. Ryk, the conserved repulsive Wnt receptor, was also induced in the lesion area, and Ryk immunoreactivity was found on the lesioned CST axons. Wnt4, which attracts ascending sensory axons in development, was acutely induced in areas closer to the lesion than Wnt1 and Wnt5a. Injection of function-blocking Ryk antibodies into the dorsal bilateral hemisectioned spinal cord either prevented the retraction of CST axons or promoted their regrowth but clearly enhanced the sprouting of CST collateral branches around and beyond the injury site. Therefore, repulsive Wnt signaling may be a cause of cortical spinal tract axon retraction and inhibits axon sprouting following injury.