人类特有基因miR-941在神经细胞中的分子功能研究

发达的大脑是人类进化的最显著特征，大脑进化的遗传学基础是生命科学的根本问题，而人类特有基因可能是大脑进化中的重要遗传因素。miR-941基因是我们发现和报道的第一个人类特有小RNA基因。前期研究发现miR-941在脑部表达，它的过量表达引起人类神经祖细胞的形态变化,其重要功能可能与神经细胞相关。本项目中，我们拟利用慢病毒感染，在人类神经细胞和其他参照细胞中过表达和用小RNA sponge（海绵）抑制其功能，观察miR-941在细胞水平对神经细胞增殖、分化、凋亡、迁移及轴突树突发生的影响；进而在分子水平鉴定其靶基因、功能基因通路和调控的分子机制；并利用转基因小鼠在器官水平探索miR-941在体内环境大脑发育时间和结构上的作用。从这些方面揭示miR-941在神经细胞和大脑发育中的功能和分子调控机制，为解析人类特有基因在人类大脑进化中的贡献提供生物学证据。

Advanced brains are the most significant feature in human evolution. The genetic basis of brain evolution is one of the fundamental questions in life sciences. Human-specific genes may play important roles in shaping human brain evolution. miR-941 was identified as the first microRNA gene ever reported. Our studies showed that miR-941 expresses in human brain and its over-expression caused phenotypic changes in human neural progenitor cells which indicated that it may display pivotal functionality in neural cells. In this project, we are going to (1) at the cellular level, use lentivirus to over-express miR-941 or inhibit it by adopting its sponge in human neural progenitor cells and other reference cell lines, to study its roles in cell propagation, differentiation, apoptosis, migration and axon and dendrite formation (2) at the molecular level, identify its target genes, the gene pathway(s) involved and the molecular mechanism of regulation, and (3) at the systematic level, manipulate transgenic mice to understand if miR-941 affects brain development spatially or temporally in vivo. From these aspects, we may disclose miR-941 functions and its molecular regulatory mechanism in neural cells and thus provides experimental evidence of the contribution of human-specific genes to human brain evolution.