Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors
Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors
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DOI：
10.1242/dev.072587
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发表时间：
2011-11-15
期刊：
影响因子：
4.6
通讯作者：
Brand, Michael
中科院分区：
文献类型：
--
作者：
Kroehne, Volker;Freudenreich, Dorian;Brand, Michael
成年哺乳动物中枢神经系统的严重创伤性损伤导致终身功能丧失。相比之下，几种非哺乳类脊椎动物物种，包括成年斑马鱼，具有再生受损器官（包括CNS）的显著能力。然而，能够或阻止CNS再生的细胞和分子机制在很大程度上是未知的。为了研究成年斑马鱼的脑再生机制，我们开发了一种创伤性损伤试验，分析了细胞对损伤的反应，并表明成年斑马鱼可以有效地再生脑损伤，并且没有永久性胶质瘢痕。使用Cre-loxP为基础的遗传谱系追踪，我们证明，her4.1阳性的心室放射状胶质祖细胞的反应损伤，增殖和产生神经母细胞迁移到病变部位。新生成的神经元存活超过3个月，被突触接触装饰并表达成熟的神经元标记物。因此，成年斑马鱼脑创伤性损伤后的再生有效地发生从放射状神经胶质型干/祖细胞。
Severe traumatic injury to the adult mammalian CNS leads to life-long loss of function. By contrast, several non-mammalian vertebrate species, including adult zebrafish, have a remarkable ability to regenerate injured organs, including the CNS. However, the cellular and molecular mechanisms that enable or prevent CNS regeneration are largely unknown. To study brain regeneration mechanisms in adult zebrafish, we developed a traumatic lesion assay, analyzed cellular reactions to injury and show that adult zebrafish can efficiently regenerate brain lesions and lack permanent glial scarring. Using Cre-loxP-based genetic lineage-tracing, we demonstrate that her4.1-positive ventricular radial glia progenitor cells react to injury, proliferate and generate neuroblasts that migrate to the lesion site. The newly generated neurons survive for more than 3 months, are decorated with synaptic contacts and express mature neuronal markers. Thus, regeneration after traumatic lesion of the adult zebrafish brain occurs efficiently from radial glia-type stem/progenitor cells.