School of Life Science, Nantong Laboratory of Development and Diseases; Second Affiliated Hospital; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Exp Neurol. 2022 Feb;348:113944. doi: 10.1016/j.expneurol.2021.113944. Epub 2021 Dec 9.
Fibroblast growth factor binding protein 3 (Fgfbp3) have been known to be crucial for the process of neural proliferation, differentiation, migration, and adhesion. However, the specific role and the molecular mechanisms of fgfbp3 in regulating the development of motor neurons remain unclear. In this study, we have investigated the function of fgfbp3 in morphogenesis and regeneration of motor neuron in zebrafish. Firstly, we found that fgfbp3 was localized in the motor neurons and loss of fgfbp3 caused the significant decrease of the length and branching number of the motor neuron axons, which could be partially rescued by fgfbp3 mRNA injection. Moreover, the fgfbp3 knockdown (KD) embryos demonstrated similar defects of motor neurons as identified in fgfbp3 knockout (KO) embryos. Furthermore, we revealed that the locomotion and startle response of fgfbp3 KO embryos were significantly restricted, which were partially rescued by the fgfbp3 overexpression. In addition, fgfbp3 KO remarkably compromised axonal regeneration of motor neurons after injury. Lastly, the malformation of motor neurons in fgfbp3 KO embryos was rescued by overexpressing drd1b or neurod6a, respectively, which were screened by transcriptome sequencing. Taken together, our results provide strong cellular and molecular evidence that fgfbp3 is crucial for the axonal morphogenesis and regeneration of motor neurons in zebrafish.
成纤维细胞生长因子结合蛋白 3（Fgfbp3）对于神经增殖、分化、迁移和黏附的过程至关重要。然而，fgfbp3 在调节运动神经元发育中的具体作用和分子机制仍不清楚。在这项研究中，我们研究了 fgfbp3 在斑马鱼运动神经元形态发生和再生中的功能。首先，我们发现 fgfbp3 定位于运动神经元中，fgfbp3 的缺失导致运动神经元轴突的长度和分支数量显著减少，而 fgfbp3 mRNA 注射可部分挽救这一现象。此外，fgfbp3 敲低（KD）胚胎表现出与 fgfbp3 敲除（KO）胚胎中相同的运动神经元缺陷。进一步的研究表明，fgfbp3 KO 胚胎的运动和惊跳反应受到明显限制，而过表达 fgfbp3 可部分挽救这一现象。此外，fgfbp3 KO 显著影响了运动神经元的轴突再生。最后，通过转录组测序筛选出的 drd1b 或 neurod6a 的过表达分别挽救了 fgfbp3 KO 胚胎中运动神经元的畸形。综上所述，我们的研究结果提供了强有力的细胞和分子证据，表明 fgfbp3 对于斑马鱼运动神经元的轴突形态发生和再生至关重要。
