项目名称: 锌指蛋白Zbtb20对大脑新皮质浅层投射神经元的发育调控作用及其机理研究
项目编号: No.31470759
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 生物科学
项目作者: 谢志芳
作者单位: 中国人民解放军第二军医大学
项目金额: 85万元
中文摘要: 大脑新皮质发育异常会导致癫痫、心智发育障碍等多种神经、精神疾病,然而目前对调控新皮质浅层投射神经元的分化和发育的分子机制尚不十分清楚。锌指蛋白Zbtb20 是申请人所在课题组自主发现并率先报道的新型转录因子,我们前期的工作表明该分子在新皮质浅层投射神经元产生的高峰期表达于小鼠端脑背侧的脑室层和脑室下层。为了揭示其体内生物学作用, 我们成功建立了神经系统特异性Zbtb20基因敲除小鼠,发现该小鼠模型的新皮质浅层变薄且细胞排列紊乱、浅层特异性分子标志的表达模式发生改变以及胼胝体内出现异位神经元等异常表型,提示Zbtb20对浅层投射神经元的发育具有重要的调控作用。在此基础上,本课题拟利用该基因敲除小鼠模型,深入分析Zbtb20对新皮质浅层投射神经元的增殖、分化、迁移以及存活的影响,同时筛选和验证其下游的重要靶基因,以明确该分子调控新皮质发育的细胞学和分子生物学机制,可望形成原创性科研成果。
中文关键词: 转录因子;神经发育;细胞分化;基因敲除小鼠
英文摘要: Abnormalities in neocortical development are common etiologies in epilepsy and cognitive disorders. Up to now, the molecular mechanism controlling the development of the Upper-layer cortical projection neurons remains unclear. Our preliminary data showed that zinc finger protein Zbtb20 was highly expressed in the ventricular zone and subventricular zone of murine dorsal developing telencephalon starting from embryonic day 14.5. Nervous system-specific Zbtb20 conditional knockout mice exhibited a decreasing in the cortical upper layer thickness with an altered morphology, an abnormal expression pattern of upper-layer specific molecular markers, and ectopic neurons in the corpus callosum. These phenotypes imply that Zbtb20 play an important role in the development of upper-layer cortex. To reveal the role and underlying mechanisms of Zbtb20 in the development of upper-layer projection neurons, in this project, we plan to analyze the proliferation, differentiation, migration and apoptosis of projection neurons in the Zbtb20-deleted developing neocortex. We will go further to screen and confirm Zbtb20's critical target genes and underlying molecular mechanisms. We believe that this project will shed new light on the understanding of neocortical development
英文关键词: transcription factor;neuron development;cell differentiation;gene knockout mice