Transcription factor Sox11b is involved in spinal cord regeneration in adult zebrafish.
Transcription factor Sox11b is involved in spinal cord regeneration in adult zebrafish.
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DOI：
10.1016/j.neuroscience.2010.10.026
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发表时间：
2011-01-13
期刊：
影响因子：
3.3
通讯作者：
Schachner M
中科院分区：
文献类型：
--
作者：
Guo Y;Ma L;Cristofanilli M;Hart RP;Hao A;Schachner M
成年斑马鱼有能力从脊髓损伤中恢复，并显示出从脑干到脊髓的下行轴突的重新生长。我们利用基因芯片进行基因表达分析，寻找脊髓损伤后的损伤诱导基因，发现Sox11b基因在损伤后11天表达上调。然而，Sox11b与再生的功能相关性尚不清楚。在这里，我们报道脊髓损伤后Sox11b基因的上调主要定位于中央管内的室管膜细胞和新分化的神经元前体或未成熟神经元。使用体内基于吗啡的基因敲除方法，我们证明了Sox11b对于脊髓损伤后的运动恢复是必不可少的。在损伤脊髓中，参与内源性神经干细胞自我更新和细胞命运决定的神经干细胞相关基因Nestin和原神经基因Ascl1a(Mash1a)的表达分别受Sox11b的调控。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测定和再生神经发生。上调Sox11b的表达以促进损伤后内源性神经干细胞的增殖和神经源性测定，可能是哺乳动物脊髓损伤后恢复治疗的一种有前景的策略。
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.
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