The role of NFI genes in glial cell fate determination

NFI基因在胶质细胞命运决定中的作用

• 批准号: 7114063
• 负责人: Benjamin Deneen
• 金额: $ 4.63万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114063
• 关键词: RNA interference; astrocytes; cell differentiation; chick embryo; developmental genetics; developmental neurobiology; embryo /fetus tissue /cell culture; functional /structural genomics; gene expression; genetic manipulation; genetic regulation; genetically modified animals; laboratory mouse; nerve /myelin protein; neurogenesis; nuclear proteins; oligodendroglia; postdoctoral investigator; protein protein interaction; protein structure function; spinal cord; transcription factor; transfection

DESCRIPTION (provided by applicant): Gene expression profiling of neural progenitor populations revealed that Nuclear Factor I (NFI) family genes are specifically expressed in glial progenitors in the developing spinal cord. Preliminary data suggests that NFI genes could be required for the generation of astrocytes in vivo. The goals of this study are to assess whether NFI genes are indeed required for the generation of astrocytes and to elucidate mechanisms that govern the ability of NFI genes to promote astrocytes. To examine whether NFI genes are required for the generation of astrocytes I will utilize both gain-and-loss of function analysis in the embryonic chick spinal cord and I will analyze astrocyte development in NFI mutant mice. Olig2 has been shown to suppress the generation of astrocytes, thus I will assess whether Olig2 can suppress the ability of NFI genes to promote astrocytes using in vitro culture systems and ectopic expression in the embryonic chick. If there is a antagonistic relationship between NFI genes and Olig2 I will investigate whether any biochemical relationship exists between these proteins. Lastly, given that Olig2 can both suppress astrocytes and oligodendrocytes, I will determine whether NFI gene function is epistatic to Olig2 in regard to the suppression of astrocytes and the promotion of oligodendrocytes, or whether NFI can uncouple these roles of Olig2. These experiments will rely on gain-and loss of function analysis in ovo, in vitro, and in mutant mice.

描述（由申请人提供）：神经祖细胞群的基因表达谱揭示核因子I（NFI）家族基因在发育中的脊髓的神经胶质祖细胞中特异性表达。初步数据表明 NFI 基因可能是体内星形胶质细胞生成所必需的。本研究的目的是评估 NFI 基因是否确实是星形胶质细胞生成所必需的，并阐明控制 NFI 基因促进星形胶质细胞能力的机制。为了检查星形胶质细胞的生成是否需要 NFI 基因，我将利用胚胎鸡脊髓的功能获得和丧失分析，并分析 NFI 突变小鼠的星形胶质细胞发育。 Olig2已被证明可以抑制星形胶质细胞的生成，因此我将使用体外培养系统和雏鸡中的异位表达来评估Olig2是否可以抑制NFI基因促进星形胶质细胞的能力。如果NFI基因和Olig2之间存在拮抗关系，我将研究这些蛋白质之间是否存在任何生化关系。最后，鉴于Olig2既可以抑制星形胶质细胞又可以抑制少突胶质细胞，我将确定NFI基因功能在星形胶质细胞的抑制和少突胶质细胞的促进方面是否对Olig2具有上位性，或者NFI是否可以解开Olig2的这些作用。这些实验将依赖于卵内、体外和突变小鼠的功能获得和丧失分析。