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育中发挥关键作用。最近对发育中耳蜗中 FGF 受体的研究数据表明，内耳感觉上皮的一组神经胶质样支持细胞（支柱细胞）的分化需要特定的 FGF 受体 FGFR3。该系统具有独特的优势，具有高度定型的神经胶质样细胞群，可以轻松识别。该提案中概述的实验将有助于进一步了解控制这种重要类型支持细胞分化的分子机制，其具体目标如下。 1. 确定柱状细胞首次需要 Fgfr3 的发育时间。 2. 检查具有组成型激活突变的小鼠的柱细胞发育。 3. 检查候选FGFR3配体在发育中耳蜗中的表达。 4.考察不同发育阶段内毛细胞消除FGF8对柱状细胞分化的影响。 5.确定FGF8是否能促进柱状细胞分化。我们提出的研究将加深我们对 FGF-FGFR 信号在耳蜗分化表型的发育和维持中的作用的理解；我们的长期目标是利用这些信息更好地了解该系统的先天性缺陷，并最终促进其修复。