Gfil in sensory neuron and hair cell development

描述(由申请人提供)：这项建议是为了审查以下想法： A)Gfi1在神经发生和内耳毛细胞发育中发挥作用 Gfi1的功能在发育过程中是保守的，因此它相互作用 使用Math1，以及C)该交互是规范所必需的，并且 哺乳动物胚胎发育过程中内耳毛细胞的发育 成年哺乳动物毛细胞的产生和修复。第一个目标是表明 GFI1对于内耳的正常发育是必需的。突变的小鼠 GFI1将接受感觉神经元和内耳毛细胞缺陷检查。这个 第二个目标是显示Gfi1在功能上与Math1在 发育保守途径。Math1突变体中GFI1的表达分析 小鼠，特别是内耳的毛细胞前体可以提供这样的功能 证据。此外，还将评估Math1在Gfi1小鼠中的表达。这个 第三个目标是检查Math1和Gfi1在头发中发挥作用的能力 内耳中细胞的产生和修复。Gfi1基因的表达构建 和Math1已经被产生了。这些构建物将被转化为 庆大霉素处理和未处理的耳蜗囊外植体 组合(S)在生成和再生毛细胞方面最有效。这个 毛细胞的生成/修复及其感觉毛发的成熟 束状物将通过显微镜进行测定。这在临床上具有重要意义，因为 基于基因治疗的方法治疗内耳毛细胞丢失或损伤 为听力和平衡受损的人提供大量的应用。

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.