Ohnmacht Jochen, Yang Yujie, Maurer Gianna W, Barreiro-Iglesias Antón, Tsarouchas Themistoklis M, Wehner Daniel, Sieger Dirk, Becker Catherina G, Becker Thomas
Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
Centre for Neuroregeneration, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK
Development. 2016 May 1;143(9):1464-74. doi: 10.1242/dev.129155. Epub 2016 Mar 10.
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.
在成年斑马鱼中，相对静止的祖细胞会在损伤诱导下生成运动神经元。受精后48小时（hpf），源自脊髓运动神经元祖域（pMN）的发育性运动神经元生成急剧下降。此后，大多是从同一区域生成少突胶质细胞。我们在此证明，在脊髓损伤后48小时内或在72 hpf时对运动神经元进行特定基因消融后，pMN域会恢复生成运动神经元，而少突胶质细胞生成则会减少。相比之下，背侧Pax2阳性中间神经元的生成没有改变。与成年再生类似，多巴胺能药物可以促进幼体运动神经元的再生。我们利用幼体损伤表明，对先天免疫系统的细胞反应进行药理学抑制会抑制运动神经元再生。因此，我们建立了一种快速的幼体再生模式。机械损伤或运动神经元消融都足以揭示pMN祖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运动神经元再生的重要影响。
