Genetic Regulation of Cochlear Development

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PROJECT SUMMARY The mammalian inner ear contains six sensory organs specialized for hearing and balance. They derive from prosensory patches that arise at unique locations in the developing inner ear and then receive patterning signals that cause them to develop into vestibular organs (cristae and maculae) or the auditory organ of Corti. Our lab and others have identified some of the signals that drive these inductive and patterning events, such as the Notch, BMP, Fgf, and Shh pathways. It is increasingly clear that dysfunction of these pathways can also lead to developmental ear defects and hearing disorders in humans. However, despite the progress that has been made in understanding these signals in the ear, fundamental questions remain about how they regulate sensory organ induction and patterning. Moreover, it is likely that many other genes and pathways that regulate ear development have still to be identified. The goals of this proposal are to use new genetic tools and advances in single cell transcriptome analysis to understand the mechanism by which Notch and BMP signaling generate and pattern inner ear sensory organs (Aims 1 and 2), and to leverage existing resources at Baylor College of Medicine to search for new genes that regulate ear development and function (Aim 3).