BACKGROUND Despite conserved developmental processes and organization of the vertebrate central nervous system, only some vertebrates including zebrafish can efficiently regenerate neural damage including after spinal cord injury. The mammalian spinal cord shows very limited regeneration and neurogenesis, resulting in permanent life-long functional impairment. Therefore, there is an urgent need to identify the cellular and molecular mechanisms that can drive efficient vertebrate neurogenesis following injury. A key pathway implicated in zebrafish neurogenesis is fibroblast growth factor signaling. METHODS In the present study we investigated the roles of distinct fibroblast growth factor members and their receptors in facilitating different aspects of neural development and regeneration at different timepoints following spinal cord injury. After spinal cord injury in adults and during larval development, loss and/or gain of Fgf signaling was combined with immunohistochemistry, in situ hybridization and transgenes marking motor neuron populations in in vivo zebrafish and in vitro mammalian PC12 cell culture models. RESULTS Fgf3 drives neurogenesis of Islet1 expressing motor neuron subtypes and mediate axonogenesis in cMet expressing motor neuron subtypes. We also demonstrate that the role of Fgf members are not necessarily simple recapitulating development. During development Fgf2, Fgf3 and Fgf8 mediate neurogenesis of Islet1 expressing neurons and neuronal sprouting of both, Islet1 and cMet expressing motor neurons. Strikingly in mammalian PC12 cells, all three Fgfs increased cell proliferation, however, only Fgf2 and to some extent Fgf8, but not Fgf3 facilitated neurite outgrowth. CONCLUSIONS This study demonstrates differential Fgf member roles during neural development and adult regeneration, including in driving neural proliferation and neurite outgrowth of distinct spinal cord neuron populations, suggesting that factors including Fgf type, age of the organism, timing of expression, requirements for different neuronal populations could be tailored to best drive all of the required regenerative processes.

中文翻译：

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不同的Fgfs在调节斑马鱼脊髓损伤后的神经发生中具有不同的作用。

背景技术尽管保守了脊椎动物中枢神经系统的发育过程和组织，但包括斑马鱼在内的仅某些脊椎动物能够有效地再生神经损伤，包括在脊髓损伤后。哺乳动物脊髓显示出非常有限的再生和神经发生，导致永久性终生功能受损。因此，迫切需要鉴定在损伤后可以驱动有效的脊椎动物神经发生的细胞和分子机制。涉及斑马鱼神经发生的关键途径是成纤维细胞生长因子信号转导。方法在本研究中，我们研究了成纤维细胞生长因子成员及其受体在促进脊髓损伤后不同时间点神经发育和再生的不同方面的作用。在成年脊髓损伤后和幼虫发育过程中，Fgf信号的丢失和/或获得与免疫组织化学，原位杂交和转基因相结合，在体内斑马鱼和体外哺乳动物PC12细胞培养模型中标记运动神经元群体。结果Fgf3驱动表达Islet1的运动神经元亚型的神经发生，并介导表达cMet的运动神经元亚型的轴突发生。我们还证明，Fgf成员的作用并不一定是概括发展的简单过程。在发育过程中，Fgf2，Fgf3和Fgf8介导表达Islet1的神经元的神经发生以及表达Islet1和cMet的运动神经元的神经元发芽。引人注目的是，在哺乳动物PC12细胞中，所有三个Fgfs均能促进细胞增殖，但是，只有Fgf2和Fgf8在一定程度上促进了神经突的生长。