Reelin与小脑发育——Notch1信号通路的调节作用

Reelin and the cerebellar development—— the regulatory effect of Notch1 signaling pathways

目的探讨Reelin在小脑放射状胶质细胞、神经干细胞和普肯耶细胞迁移和分布中的作用,并探讨Notch信号通路在其中的作用。方法取WT小鼠和reeler小鼠胚胎9d至生后60d的脑部共148例,运用免疫荧光技术检测两组小鼠小脑发育中放射状胶质细胞、神经干细胞、普肯耶细胞及激活型Notch1受体的表达。结果Reeler小鼠小脑发育中放射状胶质细胞极性紊乱导致迁移阻滞于内颗粒层,过早分化,分子层中数量减少(P<0.01);Sox2阳性的干细胞启动迁移较慢,随后未得到适当的终止信号越过普肯耶细胞层进入外颗粒层,野生型小鼠该细胞并不迁移进入外颗粒层;普肯耶细胞多数不能迁移至分子层大量阻滞于内颗粒层中形成细胞团;激活型的Notch1受体在reeler小鼠小脑中表达减少。结论 Reelin在小脑神经干细胞、胶质细胞、普肯耶细胞发育和片层化分布中有重要作用,并且Notch1信号通路参与Reelin介导的小脑发育。

Objective To investigate the effect of Reelin on the neural migration,distribution of radial glial cells,cell migration and Purkinje cells＇ development in the cerebellum,and to discuss. Regulatory effects of Notch signaling pathways. Methods A total of 148 wild-type（ WT） and reeler mice from E9（ embryonic day 9） to P60（ postnatal day60） were used for immunofluoresent labeling to visualize,the radial glial cells,neural stem cells,Purkinje cells and Notch1 positive cell in the developing cerebellum. Results Comparing with WT mice,in reeler mice,the orientations of radial glial cells（ putative Bergmann cell） were disordered with number decrease（ P〈0. 01）. The cell bodies of Bergmann cells did not move into their proper position and lingered around in internal granular layer（ IGL）. Sox2-positive stem cells in external granular layer migrated into internal granular layer with time-lag. Purkinje cells did not reach their destination and accumulated in internal granular layer. We found that Notch1 positive cells reduced in reeler mice. Conclusion Reelin plays an important role in the development of radial glial cells（ Bergmann cells）,cell migration and neural proliferation. In addition,Notch1 signaling pathway is involved in cerebellar development,via the regulation to Reelin pathway.