miR-9和miR-124在神经元发育过程中协同作用的研究

项目名称： miR-9和miR-124在神经元发育过程中协同作用的研究

项目编号： No.31201094

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 发育生物学与生殖生物学

项目作者： 薛茜

作者单位： 中国人民解放军第四军医大学

项目金额： 24万元

中文摘要： 人脑是自然界最复杂的物体之一，神经系统结构和功能的复杂及精密决定了它在胚胎发育中将经历极其精细的构建过程。神经元是构成神经系统结构和功能的基本单位，与胶质细胞一起产生感觉、行为和高级精神活动。miR-9和miR-124是哺乳动物神经系统特异表达的两种miRNA，在体外能诱导皮肤成纤维细胞向神经元转化，而单独一种miRNA没有这种作用。说明它们在神经元的分化过程中有协同作用。尽管一些miR-9或miR-124与其靶分子的相互作用已经被鉴定，但是其确切功能及协同作用尚不完全清楚。我们预测发现Ras/Rap可能是miR-9和miR-124协同调控神经元发育的信号通路之一。本课题拟在已构建的miR-9-124转基因小鼠基础上，通过体内外研究，探寻miR-9和miR-124在神经元发育中的协同作用，寻找潜在靶基因，明确信号通路，阐明其在神经元发育过程中的功能和机制，为探索神经元发育的机制提供新的思路

中文关键词： miR-9；miR-124；神经元；树突分支；协同作用

英文摘要： The human brain perhaps is the most complex object in our known universe. In the embryo development, the nervous system experiences the precise construction processe, which is determined by the complexity and precision of structure and functions. Neurons, the basic unit of the nervous system structure and functions, and glia produce sensations, behaviors and higher order mental processes. miR-9 and miR-124 are specifically expressed in the mammalian nervous system. That expression of them in human fibroblasts induces their conversion into neurons, as expressing these miRNAs separately did not lead to the conversion. These show that miR-9 and miR-124 have the synergistic effects on the neural development. Although several miRNA-target interactions have been well established, but the precise roles and synergistic effects of them remain to be further elucidated. We predict that Ras/Rap maybe one of the signal pathways for neuronal development. In this study, based on the miR-9-124 transgenic mice, we plan to investigate the synergistic effects of miR-9 and miR-124 on the neuronal development in vitro and in vivo, find the potential targets and the signal pathways and elucidate the regulation mechanisms of miR-9 and miR-124. The study will provide a new thinking for comprehensive further exploration of the neuronal

英文关键词： miR-9；miR-124；neuron；dendritic branching；synergism