神经损伤诱导蛋白2（Ninj2）在髓鞘发育及损伤修复中的作用

髓鞘是维持神经系统正常生理功能的重要组成部分。Ninj2 (Ninjurin 2) 是细胞表面粘附蛋白，其在中枢神经系统中的具体功能未见报道。实验发现，Ninj2在少突胶质细胞中大量表达。其表达水平在未成熟少突胶质细胞中较高，随细胞成熟而下降。在少突胶质细胞发育过程中，Ninj2诱导细胞增殖，抑制分化；同时Ninj2促进成熟少突胶质细胞凋亡。RNA-seq分析显示，Ninj2参与了细胞周期的调控而影响了细胞增殖与分化；并且上调内质网应激相关基因的表达而诱导细胞凋亡。动物实验显示在小鼠少突胶质细胞中特异性敲除Ninj2基因能够使髓鞘提前发育，并促进溶血卵磷脂（LPC）诱导髓鞘损伤后修复。在此基础上，我们将运用体内外实验系统，深入研究Ninj2影响少突胶质细胞发育的内在机制，分析其参与的信号通路，阐明其作用的分子机理，并探讨Ninj2及其作用相关的信号通路作为脱髓鞘疾病的治疗靶点的可能性。

Myelin sheath is an essential structure to maintain the proper physiological function of nervous system. Ninj2 (Ninjurin 2) is a cell surface adhesion protein, and its function in the central nervous system has not been reported. Ninj2 abundantly expresses in the oligodendrocytes, its expression peaks at immature oligodendrocytes, and decreases during oligodendrocyte maturation. In the oligodendrocyte lineages, despite its initial induction on proliferation of the oligodendrocyte precursor cells (OPCs), Ninj2 inhibits differentiation of OPCs. Moreover, Ninj2 induces cell apoptosis in the mature oligodendrocytes (mOLs), therefore significantly reduces cell number. RNA-seq analysis reveals that overexpression of Ninj2 affects oligodendrocytes proliferation and differentiation by its involvement in the regulation of mitotic cell cycle. And it also suggests that Ninj2 induces apoptosis of mOLs by upregulation of the genes involved in endoplasmic reticulum (ER) stress. In vivo experiments show that loss of Ninj2 gene in oligodendrocyte lineages promotes myelin development, as well as the remyelination process after LPC-induced demyelination. On this basis, we will perform further studies both in vitro and in vivo, to investigate the underpinning of the regulation on oligodendrocytes development by Ninj2. Further, we will attempt to explore the therapeutic potential of targeting Ninj2 and its related regulation pathways for demyelination diseases.