Biotechnology Center and DFG-Research Center for Regenerative Therapies Dresden, Technische Universitat Dresden, Tatzberg 47/49, 01307 Dresden, Germany.
Development. 2011 Nov;138(22):4831-41. doi: 10.1242/dev.072587. Epub 2011 Oct 17.
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.
成年哺乳动物中枢神经系统受到严重创伤会导致终身丧失功能。相比之下，几种非哺乳动物脊椎动物，包括成年斑马鱼，具有显著的再生受伤器官的能力，包括中枢神经系统。然而，允许或阻止中枢神经系统再生的细胞和分子机制在很大程度上尚不清楚。为了研究成年斑马鱼的大脑再生机制，我们开发了一种创伤性损伤测定法，分析了细胞对损伤的反应，并表明成年斑马鱼能够有效地再生脑损伤，并且没有永久性的神经胶质瘢痕形成。使用基于 Cre-loxP 的遗传谱系追踪，我们证明了 her4.1 阳性室管膜放射状胶质祖细胞对损伤反应，增殖并产生迁移到损伤部位的神经母细胞。新产生的神经元存活超过 3 个月，被突触接触标记，并表达成熟的神经元标记物。因此，成年斑马鱼大脑创伤性损伤后的再生是从放射状胶质型干细胞/祖细胞有效发生的。
