DEVELOPMENT OF THE XENOPUS ACOUSTICO-VESTIBULAR SYSTEM

描述：这项研究的目标是获得一个完整的观点 感觉器官发育和成熟的基础机制 内耳的。实验将集中在听觉和前庭 非洲爪哇两栖动物毛细胞。拟议的研究将 利用Xenopus作为经典系统提供的优势 发展研究。内耳的钾通道将是一种 这些调查的中心主题，并将被用来检验假设 关于毛细胞的发育和分化。这样做的一个主要目标是 本研究旨在建立大鼠脑内钾通道基因表达模式 发育中的内耳。电生理方法(膜片钳)将 用于研究分离毛细胞的离子通道功能。分子 将使用克隆耳部钾通道的技术(RT-PCR、RACE、 重组DNA)，并将与解剖学方法相结合(原位 杂交)，以检测耳朵中钾通道mRNA的表达。这个 这项研究的具体目的是检验以下假设：(1)一个 与drk1同源的外向钾通道在非洲爪鼠体内表达 内耳，(2)非洲爪蛙囊状毛细胞束的形态可以 与球囊毛细胞电膜特性相关，(3) 非洲爪蛙球囊毛细胞表达的离子通道类型随着 毛细胞发育，(4)不同毛发的离子诱导剂特性不同 非洲爪蛙球囊、两栖和基底乳头的细胞。 实验结果有望从根本上加深对 毛细胞多样性的遗传基础，以及关于毛细胞多样性的遗传控制 耳朵发育。这项研究的长期目标是为 为未来的研究奠定基础，这些研究将确定基因如何在 耳朵在发育和再生过程中受到调节。这些措施的结果 调查将提供基本的知识，可以用来开发 对听力损失的有效治疗，如由创伤或 遗传性疾病。

DESCRIPTION: The goal of this research is to gain an integrated view of the mechanisms that underlie development an, maturation of the sensory endorgans of the inner ear. Experiments will focus on the auditory and vestibular hair cells of the amphibian, Xenopus laevis. The proposed research will exploit the advantages that Xenopus offers as a classical system for developmental studies. The potassium channels of the inner ear will be a central subject of these investigations, and will be used to test hypotheses about hair cell development and differentiation. A major objective of this research is to establish the pattern of potassium channel gene expression in the developing inner ear. Electrophysiological methods (patch clamp) will be used to study ion channel function in dissociated hair cells. Molecular techniques will be used to clone ear potassium channels (RT-PCR, RACE, recombinant DNA) and will be combined with anatomical methods (in situ hybridization) to examine potassium channel mRNA expression in the ear. The specific aims of this research are to test the following hypotheses: (1) An outward potassium channel homologous to drkl is expressed in the Xenopus inner ear, (2) Xenopus saccular hair cell bundle morphology can be correlated with saccular hair cell electrical membrane properties, (3) The types of ion channels expressed in Xenopus saccular hair cells change as hair cells develop, (4) The properties of ion charmers differ between hair cells of the Xenopus sacculus, amphibian papilla, and basilar papilla. Experimental results are expected to advance fundamental understanding about the genetic basis of hair cell diversity, and about the genetic control of ear development. The long-term goal of this research is to lay the foundation for future studies that will determine how genes expressed in the ear are regulated during development and regeneration. Results of these investigations will provide essential knowledge that can be used to develop effective treatments for hearing loss such as that caused by trauma or genetic disorders.