Gfil in sensory neuron and hair cell development

Gfil 在感觉神经元和毛细胞发育中的作用

• 批准号: 6626145
• 负责人: Deeann Wallis-Schultz
• 金额: $ 2.19万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-07-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626145
• 关键词: animal genetic material tag; auditory pathways; balance; cell proliferation; cochlea; ear hair cell; gene expression; gene therapy; genetically modified animals; gentamicins; hearing; laboratory mouse; labyrinth; microscopy; nervous system regeneration; neurogenesis; postdoctoral investigator; protein protein interaction; protein structure function; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): This proposal is to examine the ideas that: A) Gfi1 plays a role in neurogenesis and inner ear hair cell development, B) that Gfi1 function is conserved in developmental pathways such that it interacts with Math1, and C) that this interaction is required for the specification and development of inner ear hair cells during mammalian embryogenesis as well as hair cell generation and repair in adult mammals. The first goal is to show that Gfi1 is necessary for the proper development of the inner ear. Mice mutant for Gfi1 will be examined for sensory neuron and inner ear hair cell defects. The second goal is to show that Gfi1 functionally interacts with Math1 in a developmentally conserved pathway. Gfi1 expression analysis in Math1 mutant mice, particularly in the hair cell precursors of the inner ear may provide such evidence. Additionally, Math1 expression will be assessed in Gfi1 mice. The third goal is to examine the ability of Math1 and Gfi1 to play a role in hair cell generation and repair in the inner ear. Expression constructs of the Gfi1 and Math1 have been generated. These constructs will be transfected into gentamicin treated and untreated cochlear and utricular explants to test which combination(s) are most effective at generating and regenerating hair cells. The generation/repair of the hair cells and the maturation of their sensory hair bundles will be determined by microscopy. This is clinically significant as a gene therapy based approach to treat inner ear hair cell loss or damage has immense applications for the hearing and balance impaired.

描述（由申请人提供）：该建议是研究： A）GFI1在神经发生和内耳毛细胞发育中起作用，b） GFI1函数在发育途径中保守，使其相互作用 使用MATH1，c）规范需要此交互，并且 哺乳动物胚胎发生期间内耳毛细胞的发展 成人哺乳动物的毛细胞产生和修复。第一个目标是表明 GFI1对于内耳的正确发展是必要的。小鼠突变体 将检查GFI1的感觉神经元和内耳毛细胞缺陷。这 第二个目标是证明GFI1在功能上与Math1相互作用 发育保守的途径。 Math1突变体中的GFI1表达分析 小鼠，尤其是在内耳的毛细胞前体中可能会提供这样的小鼠 证据。另外，将在GFI1小鼠中评估MATH1表达。这 第三个目标是检查Math1和GFI1在头发中发挥作用的能力 内耳的细胞产生和修复。 GFI1的表达构造 和Math1已生成。这些结构将被转染到 庆大霉素治疗和未经处理的人工耳蜗和尿布外植体测试哪个 组合最有效地产生和再生毛细胞。这 毛细胞的产生/修复和感觉毛的成熟 束将通过显微镜确定。这在临床上是显着的 基于基因治疗的治疗内耳毛细胞损失或损害的方法具有 听力和平衡受损的巨大申请。