W.M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA.
Neuroscience. 2011 Jan 13;172:329-41. doi: 10.1016/j.neuroscience.2010.10.026. Epub 2010 Oct 15.
Adult zebrafish have the ability to recover from spinal cord injury and exhibit re-growth of descending axons from the brainstem to the spinal cord. We performed gene expression analysis using microarray to find damage-induced genes after spinal cord injury, and found that Sox11b mRNA is up-regulated at 11 days after injury. However, the functional relevance of Sox11b for regeneration is not known. Here, we report that the up-regulation of Sox11b mRNA after spinal cord injury is mainly localized in ependymal cells lining the central canal and in newly differentiating neuronal precursors or immature neurons. Using an in vivo morpholino-based gene knockout approach, we demonstrate that Sox11b is essential for locomotor recovery after spinal cord injury. In the injured spinal cord, expression of the neural stem cell associated gene Nestin, and the proneural gene Ascl1a (Mash1a), which are involved in the self-renewal and cell fate specification of endogenous neural stem cells, respectively, is regulated by Sox11b. Our data indicate that Sox11b promotes neuronal determination of endogenous stem cells and regenerative neurogenesis following spinal cord injury in the adult zebrafish. Enhancing Sox11b expression to promote proliferation and neurogenic determination of endogenous neural stem cells after injury may be a promising strategy in restorative therapy after spinal cord injury in mammals.
成年斑马鱼具有从脊髓损伤中恢复的能力，并表现出从脑干到脊髓的下行轴突的再生。我们使用微阵列进行基因表达分析，以找到脊髓损伤后的损伤诱导基因，发现 Sox11b mRNA 在损伤后 11 天上调。然而，Sox11b 对再生的功能相关性尚不清楚。在这里，我们报告 Sox11b mRNA 在脊髓损伤后的上调主要定位于中央管的室管膜细胞以及新分化的神经元前体或未成熟神经元中。使用体内基于 morpholino 的基因敲除方法，我们证明 Sox11b 对于脊髓损伤后的运动功能恢复是必需的。在损伤的脊髓中，神经干细胞相关基因 Nestin 和神经前体细胞基因 Ascl1a（Mash1a）的表达受到 Sox11b 的调节，这些基因分别参与内源性神经干细胞的自我更新和细胞命运特化。我们的数据表明，Sox11b 促进了成年斑马鱼脊髓损伤后内源性干细胞的神经元决定和再生神经发生。增强 Sox11b 的表达以促进损伤后内源性神经干细胞的增殖和神经发生决定可能是哺乳动物脊髓损伤后修复治疗的一种有前途的策略。
