FORMING AND PATTERNING THE VERTEBRATE INNER EAR

内耳的早期发育经历了三个阶段：外耳胎盘的形成；外耳胎盘的形态发生以形成耳囊；以及耳囊的区域模式。每个阶段的特点是不同组织之间的诱导相互作用。虽然已经有几个信号系统参与了这些阶段的控制，但成纤维细胞生长因子信号系统显然发挥着关键作用，也是本提案的重点。该项目结合了两名研究人员广泛的技术和科学专长，并使用两个动物模型来研究早期内耳发育的细胞、分子和基因控制。在目标1中，将在内耳的早期雏形上进行三组实验，以阐明内耳发育过程中涉及的细胞作用，以及诱导、形态发生和早期图案形成所必需的和充分的相互作用。在目标2中，将进行三组实验来表征成纤维细胞生长因子信号在内耳发育的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控这一过程的细胞和分子因素提供重要的新信息。此外，这些结果将为人们提供对发育出错机制的洞察，这些机制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.