GSK3β信号通路调节少突胶质前体细胞分化的机制研究

少突胶质前体细胞（OPC）分化为成熟的少突胶质细胞（OL）是神经系统中髓鞘发育的重要环节。因此，OPC分化的调控机制对于髓鞘相关疾病及髓鞘损伤后的修复治疗具有重要意义。然而目前对OPC分化的调控机制仍不完全清楚。最近研究表明GSK3β是调控细胞增殖的重要信号因子，影响神经干细胞的分化及分裂，但是否参与OPC的分化和发育还未见报道。我们前期工作表明抑制GSK3β，减少了OL细胞的特征蛋白MBP的表达，揭示GSK3β可能调节OPC的分化。本项目将综合利用western blot、免疫组化、流式细胞术、OPC原代培养，RNA干扰，Cre-Lox技术建立条件性基因敲除动物模型等多种实验技术，研究GSK3β信号如何调节OPC的分化和OL的成熟。该项目将从目前报道较少的细胞内信号通路途径着手，揭示GSK3β信号通路如何调节OPC分化和髓鞘发育，为髓鞘相关疾病及新药的筛选鉴定提供潜在的新治疗靶点。

Differentiation of oligodendrocyte precursor cells (OPC) into oligodendrocytes (OL) is a crucial step in the formation of myelin in the central nervous system. Thus, the regulatory mechanisms of OPC differentiation are very important to myelin-related diseases and the cure of myelin injuries. However, the regulatory mechanisms of OPC differentiation are still unclear. Recent researches show that GSK3β is a key signaling factor for cell proliferation, which regulates the differentiation of neural stem cells and neurogenesis. But there are no reports whether GSK3β regulates the differentiation and development of OPC. Our preliminary data showed that inhibition of GSK3β decreases MBP expression, so GSK3β may affect the differentiation of cultured OPC. In this project, we will continue to study how the GSK3β signaling pathway regulates the differentiation of OPC and the maturation of OL using combined techniques, including western blot, immunocytochemistry, flow cytometry, OPC primary culture, RNA inteference and Cre-Lox-based animal models. This project will reveal the regulatory mechanisms of GSK3β signaling pathway on OPC differentiation and myelin development from the few reported intracellular signaling pathways aspect and provide new potential treatment targets for myelin-related diseases and the new drug screening.