Gong Jie, Wang Xin, Zhu Chenwen, Dong Xiaohua, Zhang Qinxin, Wang Xiaoning, Duan Xuchu, Qian Fuping, Shi Yunwei, Gao Yu, Zhao Qingshun, Chai Renjie, Liu Dong
School of Life Science, Nantong UniversityNantong, China.
Co-innovation Center of Neuroregeneration, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong UniversityNantong, China.
Front Mol Neurosci. 2017 Aug 28;10:274. doi: 10.3389/fnmol.2017.00274. eCollection 2017.
Insulinoma-associated1a (insm1a) is a zinc-finger transcription factor playing a series of functions in cell formation and differentiation of vertebrate central and peripheral nervous systems and neuroendocrine system. However, its roles on the development of motor neuron have still remained uncovered. Here, we provided evidences that was a vital regulator of motor neuron development, and provided a mechanistic understanding of how it contributes to this process. Firstly, we showed the localization of in spinal cord, and primary motor neurons (PMNs) of zebrafish embryos by hybridization, and imaging analysis of transgenic reporter line . Then we demonstrated that the deficiency of in zebrafish larvae lead to the defects of PMNs development, including the reduction of caudal primary motor neurons (CaP), and middle primary motor neurons (MiP), the excessive branching of motor axons, and the disorganized distance between adjacent CaPs. Additionally, knockout of impaired motor neuron differentiation in the spinal cord. Locomotion analysis showed that swimming activity was significantly reduced in the -null zebrafish. Furthermore, we showed that the loss of function significantly decreased the transcript levels of both and . Microinjection of and mRNA rescued the motor neuron defects in deficient embryos. Taken together, these data indicated that regulated the motor neuron development, at least in part, through modulation of the expressions of and .
胰岛素瘤相关蛋白1a（Insm1a）是一种锌指转录因子，在脊椎动物中枢和外周神经系统以及神经内分泌系统的细胞形成和分化中发挥一系列功能。然而，其在运动神经元发育中的作用仍未被揭示。在此，我们提供证据表明Insm1a是运动神经元发育的重要调节因子，并对其如何促进这一过程提供了机制上的理解。首先，我们通过原位杂交和转基因报告系的成像分析，展示了Insm1a在斑马鱼胚胎脊髓和初级运动神经元（PMNs）中的定位。然后我们证明斑马鱼幼虫中Insm1a的缺失导致PMNs发育缺陷，包括尾侧初级运动神经元（CaP）和中间初级运动神经元（MiP）数量减少、运动轴突过度分支以及相邻CaP之间的距离紊乱。此外，敲除Insm1a会损害脊髓中运动神经元的分化。运动分析表明，Insm1a基因敲除的斑马鱼游泳活动显著减少。此外，我们表明Insm1a功能丧失显著降低了Isl1和Hb9的转录水平。显微注射Isl1和Hb9 mRNA可挽救Insm1a缺陷胚胎中的运动神经元缺陷。综上所述，这些数据表明Insm1a至少部分通过调节Isl1和Hb9的表达来调控运动神经元的发育。
