海马神经干细胞的增殖分化异常引起学习、记忆缺陷，导致智力迟钝。初级纤毛介导Shh信号通路在海马神经干细胞的形成、增殖分化中具有重要作用。最近发现调控蛋白?-arrestin 在Shh信号通路中具有重要的调控作用，但其在海马神经干细胞增殖分化中的作用及机制尚不清楚。本课题组发现小鼠海马神经干细胞中?-arrestin 2基因沉默会降低神经干细胞的增殖能力，因此提出?-arrestin 2调控初级纤毛上Shh信号通路影响海马神经干细胞增殖分化，从而调控学习和记忆的假说。本课题拟以?-arrestin 2基因沉默和?-arrestin 2基因过表达的神经干细胞为研究对象，研究?-arrestin 2对初级纤毛上Shh信号通路的调控作用，利用?-arrestin 2基因敲除小鼠在体内进一步验证其在海马神经干细胞增殖分化中的作用，为神经干细胞增殖分化的机制研究和临床治疗应用提供实验依据。

The abnormality of proliferation and differentiation of neural stem cells in hippocampus causes the defect of learning and memory. It brings about mental retardation. The primary cilium mediate Shh pathway to regulate the formation, proliferation and differentiation of neural stem cells in hippocampus. At present the regulator ?-arrestin was found very important for the Shh pathway, but the role was not known in the proliferation and differentiation of neural stem cells. We found the knockdown of ?-arrestin 2 reduced the proliferation of neural stem cells. So we put forward a hypothesis that ?-arrestin 2 regulates Shh pathway in the neural stem cells of hippocampus and affects the learning and memory of the mice. This project will first study how ?-arrestin 2 regulates Shh pathway by using the neural stem cells with ?-arrestin 2 knockdown or overexpression, then explore this role in the proliferation and differentiation of neural stem cells in hippocampus in ?-arrestin 2 knockout mice. It will provide useful information for mechanism study and for large scale expansion of neural stem cells required by potential clinical therapy.