FGF in sensory system development

FGF 在感觉系统开发中的应用

• 批准号: 7032295
• 负责人: Olivia Mary Bermingham-McDonogh
• 金额: $ 26.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7032295
• 关键词: cell differentiation; cochlea; developmental neurobiology; ear hair cell; fibroblast growth factor; gene mutation; genetically modified animals; glia; growth factor receptors; immunocytochemistry; in situ hybridization; laboratory mouse; ligands; neurogenesis; organ culture; protein tyrosine kinase; western blottings

DESCRIPTION (provided by applicant): Receptor tyrosine kinases are known to play a key role in the development of non-neuronal cells in neural tissue. Recent data from investigations of FGF receptors in the developing cochlea have shown that a specific FGF receptor FGFR3 is required for the differentiation of a group of glial-like support cells of the inner ear's sensory epithelium, the pillar cells. This system provides the unique advantage of having a highly stereotyped population of glial-like cells that can be readily identified. The experiments outlined in this proposal will lead to further understanding of the molecular mechanisms that control the differentiation of this important type of support cell, with the following specific aims. 1. To determine the time in development when Fgfr3 is first required for Pillar cells. 2. To examine pillar cell development in mice with constitutively activated mutations. 3. To examine the expression of candidate FGFR3 ligands in the developing cochlea. 4. To examine the effect on Pillar cell differentiation of elimination of FGF8 from the inner hair cells at different stages of development. 5. To determine whether FGF8 can promote pillar cell differentiation. The studies we have proposed will extend our understanding of the role of FGF-FGFR signaling in the development and maintenance of the differentiated phenotypes in the cochlea; our long term aims are to use this information to better understand congenital defects in this system and to ultimately promote its repair.

描述（由申请人提供）：已知受体酪氨酸激酶在神经组织中非神经元细胞的发展中起关键作用。来自发育中的耳蜗中FGF受体研究的最新数据表明，特定的FGF受体FGFR3是分化内耳感官上皮细胞的一组神经胶质样的支撑细胞所必需的。该系统提供了具有高度刻板印象的神经胶质样细胞的独特优势，可以很容易地识别出来。本提案中概述的实验将进一步了解控制这种重要类型的支持细胞的分化的分子机制，并具有以下特定目的。 1。确定柱细胞首先需要FGFR3的发育时间。 2。检查具有组成型活化突变的小鼠的柱细胞发育。 3。检查发育中的耳蜗中候选FGFR3配体的表达。 4。检查对不同发育阶段的内毛细胞消除FGF8的柱细胞分化的影响。 5。确定FGF8是否可以促进柱细胞分化。我们提出的研究将扩展我们对FGF-FGFR信号在耳蜗中分化表型的开发和维持中的作用的理解。我们的长期目的是使用此信息来更好地了解该系统中的先天性缺陷并最终促进其修复。