DEVELOPMENTAL REGULATION OF INNER EAR CELL FATE

The inner ear is a complex sensory organ whose function is sensitive to a number of genetic and environmental factors that lead to congenital deafness, hearing impairment, or vestibular dysfunction. An understanding of how inner ear sensory structures are formed and function will be fundamental to developing strategies to ameliorate or reverse deficits of inner ear function. The goal of this project is to identify molecular genetic pathways that control patterning and development of sensory cell structures in the inner ear. Utilizing wild-type and mutant (dog-eared, dog; that is defective in vestibular sensory epithelium formation) zebrafish embryos the following specific aims will be pursued: 1) Develop a high resolution fate map of the otic placode and early otic vesicle using the local activation of caged fluorescein. This map will identify areas of the early ear that will give rise to the five developing sensory epithelia of the 48hr otocyst. 2) Complete the characterization of the dog mutation with respect to patterns of gene expression in the developing sensory epithelia of the ear. 3) Test for cell autonomy of the dog phenotype and timing of cell commitment to the sensory epithelium fate by cell transplantations. 4) Establish mapping crosses to identify the genomic location of the dog gene. These aims will provide a detailed picture of the cell biological and molecular genetic events that precede sensory structure formation in the inner ear and lead to the eventual cloning of the dog gene.