Huang Guo-Hui, Yang Xi-Tao, Chen Kui, Xing Jin, Guo Lin, Zhu Liang, Li Hong-Jiang, Li Xin-Cai, Zhang Sheng-Yi, Feng Dong-Fu
Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Neuroscience Division, Department of Anatomy, Histology, and Embryology, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Front Cell Neurosci. 2016 Mar 31;10:85. doi: 10.3389/fncel.2016.00085. eCollection 2016.
Neural stem cell (NSC) proliferation and differentiation play a pivotal role in the development of brain, the plasticity of the brain network, and the repair for brain function in CNS diseases. The mechanisms regulating NSC behavior are not well elucidated. Previous studies showed porf-2 functions as a modulator in central nerve system development. We here show that porf-2, a conserved family of RhoGAPs, is highly and specifically expressed in NSCs. We also demonstrate that porf-2 inhibits the proliferation of NSCs in vivo and in vitro, but has no effect on NSC differentiation. We investigated which domain is required for the role of porf-2 on NSC proliferation. By using neurosphere formation and Edu assay we confirmed the GAP domain is necessary for its function. In addition, we surveyed a few classical pathways on NSC proliferation and found that porf-2 inhibits NSC proliferation by suppressing the β-catenin nuclear translocation. Taken together, we show for the first time that porf-2 inhibits NSC proliferation through Wnt/β-catenin pathway by its GAP domain.
神经干细胞（NSC）的增殖和分化在脑发育、脑网络可塑性以及中枢神经系统疾病中脑功能的修复过程中发挥着关键作用。调控神经干细胞行为的机制尚未完全阐明。先前的研究表明，porf-2在中枢神经系统发育中起调节作用。我们在此表明，porf-2作为一个保守的RhoGAP家族，在神经干细胞中高度且特异性表达。我们还证明，porf-2在体内和体外均抑制神经干细胞的增殖，但对神经干细胞的分化没有影响。我们研究了porf-2对神经干细胞增殖作用所需的结构域。通过使用神经球形成和Edu检测，我们证实GAP结构域对其功能是必需的。此外，我们研究了一些关于神经干细胞增殖的经典信号通路，发现porf-2通过抑制β-连环蛋白核转位来抑制神经干细胞的增殖。综上所述，我们首次表明porf-2通过其GAP结构域通过Wnt/β-连环蛋白信号通路抑制神经干细胞的增殖。
