FORMING AND PATTERNING THE VERTEBRATE INNER EAR

内耳的早期发育分为三个阶段：耳穴的形成；耳基体形成耳囊肿的形态发生；耳囊肿的局部图。每个阶段的特点是不同组织之间的诱导相互作用。虽然有几个信号系统参与了这些阶段的控制，但FGF信号系统显然起着关键作用，是本研究的重点。该项目结合了两位研究者广泛的技术和科学专长，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，以阐明参与内耳发育的细胞作用，以及它们的诱导、形态发生和早期模式所需和充分的相互作用。在目标2中，将进行三组实验来表征FGF信号在内耳发育这些中心事件中的作用。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素提供重要的新信息。此外，这一结果将有助于深入了解发育出错的机制，从而导致人类听觉系统的严重先天缺陷。

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.