FGF in sensory system development

描述(申请人提供)：已知受体酪氨酸激酶在神经组织中非神经细胞的发育中起关键作用。最近对发育中的耳蜗中的成纤维细胞生长因子受体的研究表明，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一种特异的成纤维细胞生长因子受体FGFR3。这个系统提供了一个独特的优势，即拥有一个高度定型的胶质样细胞群体，可以很容易地识别出来。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，具体目的如下。1.确定柱状细胞首次需要FGFR3的发育时间。2.检测成分激活突变小鼠的柱状细胞发育情况。3.检测FGFR3候选配体在发育过程中的表达。4.检测不同发育阶段内毛细胞中FGF8的去除对柱状细胞分化的影响。5.确定FGF8是否具有促进柱状细胞分化的作用。我们提出的研究将扩大我们对成纤维细胞生长因子-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中的先天性缺陷，并最终促进其修复。

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.