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）：本提案旨在审查以下想法： A）Gfi 1在神经发生和内耳毛细胞发育中起作用，B） Gfi 1的功能在发育途径中是保守的， 与数学1和C）这种相互作用是规范所必需的， 在哺乳动物胚胎发育过程中内耳毛细胞的发育以及 成年哺乳动物的毛细胞生成和修复。第一个目标是证明 Gfi 1是内耳正常发育所必需的。小鼠突变体 将检查Gfi 1的感觉神经元和内耳毛细胞缺陷。的 第二个目标是证明Gfi 1在功能上与Math 1相互作用， 发育保守的途径。Math 1突变体中的Gfi 1表达分析 小鼠，特别是内耳的毛细胞前体中的小鼠，可以提供这种 证据此外，将在Gfi 1小鼠中评估Math 1表达。的 第三个目标是检查Math 1和Gfi 1在头发中发挥作用的能力 内耳中的细胞生成和修复。Gfi 1的表达构建体 Math 1已经生成。这些构建体将被转染到 庆大霉素处理和未处理的耳蜗和椭圆囊外植体，以测试 组合在产生和再生毛细胞方面最有效。的 毛细胞的产生/修复及其感觉毛的成熟 束将通过显微镜测定。这在临床上具有重要意义， 基于基因疗法的治疗内耳毛细胞损失或损伤的方法， 对听力和平衡障碍的巨大应用。