DEVELOPMENT OF THE XENOPUS ACOUSTICO-VESTIBULAR SYSTEM

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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.