FORMING AND PATTERNING THE VERTEBRATE INNER EAR

脊椎动物内耳的形成和图案化

• 批准号: 6634501
• 负责人: GARY C SCHOENWOLF
• 金额: $ 35.25万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6634501
• 关键词: Mus musculus; biological models; chick embryo; developmental neurobiology; ectoderm; embryo /fetus; fibroblast growth factor; gene induction /repression; genetic models; histogenesis; labyrinth; optic disk; quail

The early development of the inner ear occurs in three phases: formation of the otic placode; morphogenesis of the otic placode to form the otocyst; and regional patterning of the otocyst. Each phase is characterized by inductive interactions among different tissues. Although several signaling systems have been implicated in the control of the phases, the FGF signaling system clearly plays a critical role and is a focus of this proposal. This project combines the broad technical and scientific expertise of two investigators and use two animal models to examine the cellular, molecular and genetic control of early inner ear development. In aim 1, three sets of experiments will be conducted on the early rudiments of the inner ear to elucidate the cellular plays involved in their development, and the interactions that are required as well as sufficient for their induction, morphogenesis and early patterning. In aim 2, three sets of experiments will be conducted to characterize the roles of FGF signaling in these central events of inner ear development. Collectively, these studies will provide important new information on the normal development of the inner ear and the cellular and molecular factors that regulate this process. Additionally, the results will furnish insight into mechanisms by which development goes awry, causing serious birth defects of the auditory system in humans.

内耳的早期发育分为三个阶段：耳基板的形成;耳基板的形态发生以形成耳囊;以及耳囊的区域图案化。每个阶段的特征在于不同组织之间的诱导相互作用。虽然几个信号系统已经涉及的阶段的控制，FGF信号系统显然发挥了关键作用，是这个建议的焦点。该项目结合了两名研究人员的广泛技术和科学专业知识，并使用两种动物模型来研究早期内耳发育的细胞，分子和遗传控制。在目标1中，将对内耳的早期雏形进行三组实验，以阐明其发育中涉及的细胞作用，以及诱导，形态发生和早期模式所需的相互作用。在目标2中，将进行三组实验来表征FGF信号传导在内耳发育的这些核心事件中的作用。总的来说，这些研究将为内耳的正常发育以及调节这一过程的细胞和分子因子提供重要的新信息。此外，研究结果将提供深入了解发育出错的机制，导致人类听觉系统的严重先天缺陷。