Foxg1对皮质中间神经元发育的调控机制研究

项目名称： Foxg1对皮质中间神经元发育的调控机制研究

项目编号： No.31471041

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 神经、认识与心理学

项目作者： 赵春杰

作者单位： 东南大学

项目金额： 88万元

中文摘要： 中间神经元虽然在皮层神经元中只占20%-30%的比例，但是对于维持大脑正常功能发挥着至关重要的作用。目前对于中间神经元发育和成熟的调控研究十分有限，我们前期工作提示Foxg1参与调控中间神经发育。本研究通过分别在中间神经元前体细胞、正在成熟的中间神经元中条件性敲除Foxg1，研究Foxg1缺失对中间神经元的发生、分化迁移以及成熟的影响，检测目前已知或可能参与调控中间神经元发育的转录因子如Mash1、Nkx2.1和Dlx1/2以及调控其迁移的趋化因子的改变。 利用ChIP和 Luciferase assay 检测Foxg1是否直接或间接调控上述鉴定出来的剧烈上调或下调的因子，再对Foxg1直接调控的因子进行过表达或敲减进行验证，在此基础上明确Foxg1调控中间神经元发育和成熟的分子机制。我们的研究将有助于理解中间神经元发育的调控，从而进一步探究由中间神经元异常引起的神经精神类疾病的致病机制。

中文关键词： 神经发育；中间神经元；神经元迁移；大脑皮层；细胞分化

英文摘要： Despite only comprising 20-30% of cortical neurons, the gamma-aminobutyric acid (GABA)ergic inerneurons play vital roles in modulating cortical functions, however the mechanisms underlying interneuron development remain to be elucidated. By conditional disruption of Foxg1 in progenitor cells and interneurons undergoing maturation respectively, this project aims to understand roles of Foxg1 in cell proliferation, differentiation, migration and maturation during the development of cortical interneurons. We will also detect the expression level and pattern of transcription factors such as Mash1, Dlx1/2, Nkx2.1 which have been known to be involved in interneuron development and other possible regulators after Foxg1 deletion. Meanwhile migration regulators including repulsive semaphorin 3A/F (Sema 3A/F), roundabout-1 (Robo1), EphA4 and attractive Cxcr4/7 will be examined as well. We will further try to figure out whether Foxg1 can directly or indirectly regulate the gene that is identified to be severely up-regulated or down-regulated by chromatin immunoprecipitations (ChIP) and Luciferase assay. Finally rescue experiments will be performed to further confirm the regulation of Foxg1 on its down-stream gene. Our study will help to understand the mechanisms of the development of interneurons and interneuron-related diseases such as mental disorders.

英文关键词： neurodevelopment;interneurons;neuron migration;cortex;cell differentiation