小鼠大脑皮层中ADAM17表达的降低对神经元前体细胞外向迁移的抑制作用  

Down-Regulation of ADAM17 Expression in Mouse Developing Cortex Causes Neuron Migration Defect

作　　者：潘乐[1] 马执行[1] 李擎瑜[1] 刘彬[1] 盖敏[1] 郑煜芳[1] 

机构地区：[1]复旦大学生命科学学院生理学和生物物理学系,上海200433

出　　处：《复旦学报（自然科学版）》2011年第5期597-604,F0002,F0003,共10页Journal of Fudan University：Natural Science

基　　金：国家自然科学基金资助项目(30800322);上海市浦江人才计划资助项目(08PJ1401300);复旦大学脑研究院开放课题资助项目

摘　　要：在发育过程中神经元前体细胞的外向迁移对于大脑皮层的多层结构建立有着重要作用.金属蛋白酶家族的成员ADAM17(A Disintegrin And Metalloprotease 17)对于多种膜蛋白的成熟释放有着重要作用,包括多个表皮生长因子受体的配体以及Notch等蛋白.这些底物中有多个对神经干细胞的增殖、分化、迁移都有重要作用.为了探讨ADAM17在大脑皮层发育过程中的生理作用,结合RNAi和IUE的技术,降低小鼠大脑发育阶段中ADAM17的表达.结果显示:用RNAi降低ADAM17在小鼠大脑皮层发育14—18d中的表达,会造成神经元前体细胞的外向迁移障碍,使得细胞停留在脑室下区.The migration of neuronal progenitor cells towards out layer is crucial for the multiple-layer formation of mammalian cortex during development.ADAM17（a disintegrin and metalloprotease 17） is a metalloprotease that can shed many membrane proteins including Notch and ligands of EGFR,which have important function during neural stem cells proliferation,migration,and differentiation.To explore the function of ADAM17 in cortex development,RNA interference and IUE（in utero electropration） was used to knock down the expression of ADAM17 during mice cortex development.After knocking down the expression of ADAM17 during E14 to E18 in mice,the migration of those neuronal progenitor cells towards out layer was blocked and those cells were stocked in the subventricular zone of cortex.

关 键 词：ADAM17 大脑皮层发育 神经元前体细胞 神经元外向迁移 肿瘤坏死因子α-转化酶 

分 类 号：Q189[生物学—神经生物学]