Spinal motor neurons are regenerated after mechanical lesion and genetic ablation in larval zebrafish.
Spinal motor neurons are regenerated after mechanical lesion and genetic ablation in larval zebrafish.
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DOI：
10.1242/dev.129155
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发表时间：
2016-05-01
期刊：
影响因子：
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通讯作者：
Becker T
中科院分区：
文献类型：
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作者：
Ohnmacht J;Yang Y;Maurer GW;Barreiro-Iglesias A;Tsarouchas TM;Wehner D;Sieger D;Becker CG;Becker T
在成年斑马鱼中，相对静止的祖细胞显示出损伤诱导的运动神经元的产生。受精后48 小时，来自脊髓运动神经元前体区域的发育运动神经元生成急剧下降。在此之后，大多数少突胶质细胞是从相同的区域产生的。我们在这里证明，在脊髓损伤或运动神经元以72 的频率进行特定的遗传消融后的48 小时内，PMN域恢复到运动神经元的生成，但以少突胶质细胞的生成为代价。相比之下，背侧Pax2阳性中间神经元的产生没有改变。多巴胺能药物可以促进幼虫运动神经元的再生，类似于成体的再生。我们使用幼虫损伤来表明，药物抑制先天免疫系统的细胞反应会抑制运动神经元的再生。因此，我们建立了一个快速幼虫再生的范例。无论是机械性损伤还是运动神经元消融，都足以显示PMN前体细胞具有高度的发育灵活性。此外，我们还展示了免疫系统对这些祖细胞再生运动神经元的重要影响。摘要：机械损伤或基因消融后脊髓运动神经元的再生是以少突胶质细胞形成为代价的，并受到先天免疫系统的促进。
In adult zebrafish, relatively quiescent progenitor cells show lesion-induced generation of motor neurons. Developmental motor neuron generation from the spinal motor neuron progenitor domain (pMN) sharply declines at 48 hours post-fertilisation (hpf). After that, mostly oligodendrocytes are generated from the same domain. We demonstrate here that within 48 h of a spinal lesion or specific genetic ablation of motor neurons at 72 hpf, the pMN domain reverts to motor neuron generation at the expense of oligodendrogenesis. By contrast, generation of dorsal Pax2-positive interneurons was not altered. Larval motor neuron regeneration can be boosted by dopaminergic drugs, similar to adult regeneration. We use larval lesions to show that pharmacological suppression of the cellular response of the innate immune system inhibits motor neuron regeneration. Hence, we have established a rapid larval regeneration paradigm. Either mechanical lesions or motor neuron ablation is sufficient to reveal a high degree of developmental flexibility of pMN progenitor cells. In addition, we show an important influence of the immune system on motor neuron regeneration from these progenitor cells. Summary: Regeneration of spinal motor neurons following mechanical lesion or genetic ablation occurs at the expense of oligodendrogenesis and is promoted by the innate immune system.