Myostatin is a negative regulator of adult neurogenesis after spinal cord injury in zebrafish.
Myostatin is a negative regulator of adult neurogenesis after spinal cord injury in zebrafish.
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DOI：
10.1016/j.celrep.2022.111705
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发表时间：
2022-11-22
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
神经元再生的内在和外在抑制阻碍了哺乳动物脊髓（SC）修复。相比之下，成年斑马鱼在完全SC横断后实现功能恢复。虽然先天SC再生的研究主要集中在轴突再生作为主要修复机制，但成人局部神经发生如何影响功能恢复尚不清楚。在这里，我们发现斑马鱼肌生长抑制素b （mstnb）在损伤后背SC祖细胞的生态位中的动态表达。MSTNB突变体表现出功能恢复受损，正常的神经胶质和轴突桥接在病变处，新生神经元的轮廓增加。在分子上，神经元分化基因上调，而神经干细胞维持基因fgf1b在mstnb突变体中下调。最后，我们发现人成纤维细胞生长因子1 （FGF1）治疗可以挽救mstnb突变体的分子和细胞表型。这些研究揭示了mstnb意想不到的神经发生功能，并确立了局部成人神经发生对先天SC修复的重要性。Saraswathy等人报道，在斑马鱼的脊髓再生过程中，肌生成抑制素的表达局限于一个祖细胞亚群。他们发现肌肉生长抑制素b突变体的功能恢复受损。他们发现的证据表明，myostatin-fgf1b信号调节先天脊髓修复过程中祖细胞自我更新和神经元分化的速率。
Intrinsic and extrinsic inhibition of neuronal regeneration obstruct spinal cord (SC) repair in mammals. In contrast, adult zebrafish achieve functional recovery after complete SC transection. While studies of innate SC regeneration have focused on axon regrowth as a primary repair mechanism, how local adult neurogenesis affects functional recovery is unknown. Here, we uncover dynamic expression of zebrafish myostatin b (mstnb) in a niche of dorsal SC progenitors after injury. mstnb mutants show impaired functional recovery, normal glial and axonal bridging across the lesion, and an increase in the profiles of newborn neurons. Molecularly, neuron differentiation genes are upregulated, while the neural stem cell maintenance gene fgf1b is downregulated in mstnb mutants. Finally, we show that human fibroblast growth factor 1 (FGF1) treatment rescues the molecular and cellular phenotypes of mstnb mutants. These studies uncover unanticipated neurogenic functions for mstnb and establish the importance of local adult neurogenesis for innate SC repair. Saraswathy et al. report that myostatin expression localizes to a subset of progenitor cells during spinal cord regeneration in zebrafish. They found that functional recovery is impaired in myostatin b mutants. They uncovered evidence showing that myostatin-fgf1b signaling regulates the rates of progenitor self-renewal and neuronal differentiation during innate spinal cord repair.
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