Different Fgfs have distinct roles in regulating neurogenesis after spinal cord injury in zebrafish.
Different Fgfs have distinct roles in regulating neurogenesis after spinal cord injury in zebrafish.
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DOI：
10.1186/s13064-018-0122-9
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发表时间：
2018-11-17
影响因子：
3.6
通讯作者：
Jusuf PR
中科院分区：
文献类型：
--
作者：
Goldshmit Y;Tang JKKY;Siegel AL;Nguyen PD;Kaslin J;Currie PD;Jusuf PR
尽管脊椎动物中枢神经系统的发育过程和组织结构保守，但只有包括斑马鱼在内的一些脊椎动物能够有效地再生神经损伤，包括脊髓损伤后。哺乳动物的脊髓表现出非常有限的再生和神经再生，导致永久性终身功能障碍。因此，迫切需要确定能够驱动脊椎动物损伤后高效神经发生的细胞和分子机制。斑马鱼神经发生的一个关键途径是成纤维细胞生长因子信号转导。在本研究中，我们研究了不同的成纤维细胞生长因子成员及其受体在脊髓损伤后不同时间点促进神经发育和再生的不同方面所起的作用。在体内斑马鱼和体外哺乳动物PC12细胞培养模型中，成体脊髓损伤后和幼虫发育过程中，成纤维细胞生长因子信号的丢失和/或获得与免疫组织化学、原位杂交和转基因标记运动神经元种群相结合。FGF3驱动表达运动神经元亚型的Islet1的神经发生，并在表达cMET的运动神经元亚型中介导轴突的发生。我们还证明，成长性生长因子成员的作用不一定是简单地概括发展。在发育过程中，FGF2、Fgf3和Fgf8介导了表达Islet1的神经元的神经发生和表达运动神经元的Islet1和cMET的神经元萌发。在哺乳动物PC12细胞中，三种FGFs都能促进细胞增殖，但只有FGF2和一定程度上的Fgf8促进细胞突起生长，而Fgf3没有。本研究证实了成纤维细胞生长因子成员在神经发育和成体再生中的不同作用，包括在驱动不同脊髓神经元种群的神经增殖和轴突生长方面的作用，提示包括成纤维细胞生长因子类型、生物体年龄、表达的时机、不同神经元种群的需求等因素可以被定制以最好地驱动所有必需的再生过程。
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. 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. 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. 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.
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影响因子：
56.9
作者：
Gurevich, David B.;Phong Dang Nguyen;Currie, Peter D.
通讯作者：
Currie, Peter D.
影响因子：
4.2
作者：
Huang, Ming-Chao;Lo, Ming-Jei;Cheng, Henrich
通讯作者：
Cheng, Henrich
影响因子：
16.2
作者：
Ebens, A;Brose, K;TessierLavigne, M
通讯作者：
TessierLavigne, M
影响因子：
3
作者：
Cheng, H;Liao, KK;Shih, YH
通讯作者：
Shih, YH
DOI：
10.1073/pnas.0700942104
发表时间：
2007-04-24
影响因子：
11.1
作者：
Hall, Thomas E.;Bryson-Richardson, Robert J.;Currie, Peter D.
通讯作者：
Currie, Peter D.