脑皮层干细胞分化兴奋性神经元的基因调控机制的研究

项目名称： 脑皮层干细胞分化兴奋性神经元的基因调控机制的研究

项目编号： No.81471159

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李洪

作者单位： 安徽医科大学

项目金额： 70万元

中文摘要： 兴奋性神经元是哺乳动物大脑皮层的主要组成部分，也是大脑皮层中亚型最多的神经元。其环路的形成和功能在大脑认知的功能中起决定作用。兴奋性神经元发生于端脑脑室区/亚脑室区的神经干细胞。脑室区/亚脑室区神经干细胞决定分化神经元不同亚型的基因网络调控机制目前尚不清楚。 在神经元发生期，不同类型的兴奋性神经元的生成与时间紧密关联。本项目通过对脑室区神经干细胞在神经元生成的不同时期进行了基因组水平上的比较，既比较了早期底层神经元生成期（E12）和晚期表层神经元生成期（E14）的基因组表达资料，发现了大量具有显著性差异的时间特异性表达基因，并集中对其中最具显著性的，在早期高表达的几个基因家族在神经干细胞对底层神经元命运决定的机制进行了详尽的分析，开启一条揭示决定皮层兴奋性神经元命运发生的内源性基因调控机制的研究通路。

中文关键词： 脑皮层发育；神经干细胞；兴奋性神经元；基因调控；细胞命运决定

英文摘要： The diverse subtypes of cortical excitatory projection neurons consist of the major component of cortical neurons, and neuronal circuits formed by them are fundamentals for cognitive function of the brain. Cell fate of various cortical excitatory neurons is determined in neuronal progenitors of the ventricular zone and subventricular zone (VZ/SVZ) of the telencephalon. Molecular mechanisms of generating such diverse types of projection neurons from progenitor cells in the VZ/SVZ are not known. It is believed that the generation of different types of cortical projection neurons is temporally regulated. Here we have compared transcriptome data from progenitor cells in mouse the VZ/SVZ at two different neurogenesis stages that are correspondent to time points of deep-layer neurogenesis (E12) and upper-layer neurogenesis (E14) respectively, and found amount of genes that show temporal differential expression. In this study, we focus on a few top scored temporal differential expressed genes which have high expression levels during early neurogenesis stage. We will investigate roles of these genes in cell fate determination of deep-layer neurons during early neurogenesis. This study will pave a way to uncover intrinsic genetic programs of cell fate determination in neuronal progenitor cells.

英文关键词： corticogenesis;excitatory neuron;neurogenesis;neuronal progenitor cells;cell fate determination