Wnt/ß-catenin signaling is required for radial glial neurogenesis following spinal cord injury.
Wnt/ß-catenin signaling is required for radial glial neurogenesis following spinal cord injury.
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DOI：
10.1016/j.ydbio.2015.03.025
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发表时间：
2015-07-01
影响因子：
2.7
通讯作者：
Dorsky, Richard I.
中科院分区：
文献类型：
--
作者：
Briona, Lisa K.;Poulain, Fabienne E.;Mosimann, Christian;Dorsky, Richard I.
哺乳动物脊髓损伤导致永久性感觉运动丧失，部分原因是缺乏损伤诱导的神经发生。神经元的再生依赖于常驻的神经祖细胞，在斑马鱼中，这些祖细胞以放射状胶质细胞的形式存在于整个中枢神经系统。然而，调节脊髓祖细胞的分子机制仍不清楚。Wnt/ß-catenin信号对于斑马鱼和其他脊椎动物的多种组织的再生反应是必需的，但目前尚不清楚该途径是否在脊髓再生中起作用。在这里，我们显示脊髓放射状胶质细胞在横断后发生神经发生时表现出Wnt/ß-catenin活性。然后，我们使用cre介导的谱系追踪来标记放射状胶质细胞的后代，并表明Wnt/ß-catenin信号是祖细胞分化为神经元所必需的。最后，我们发现损伤后的轴突再生也需要Wnt/ß-catenin信号，提示该通路在功能恢复中的协调作用。因此，我们的数据确定Wnt/ß-catenin通路激活是脊髓再生的必要步骤。
Spinal cord injury results in permanent sensorimotor loss in mammals, in part due to a lack of injury-induced neurogenesis. The regeneration of neurons depends upon resident neural progenitors, which in zebrafish persist throughout the central nervous system as radial glia. However the molecular mechanisms regulating spinal cord progenitors remain uncharacterized. Wnt/ß-catenin signaling is necessary for the regenerative response of multiple tissues in zebrafish as well as other vertebrates, but it is not known whether the pathway has a role in spinal cord regeneration. Here we show that spinal radial glia exhibit Wnt/ß-catenin activity as they undergo neurogenesis following transection. We then use Cre-mediated lineage tracing to label the progeny of radial glia and show that Wnt/ß-catenin signaling is required for progenitors to differentiate into neurons. Finally, we show that axonal regrowth after injury also requires Wnt/ß-catenin signaling, suggesting coordinated roles for the pathway in functional recovery. Our data thus establish Wnt/ß-catenin pathway activation as a necessary step in spinal cord regeneration.
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