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• Articles by Katherine Shim
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Sprouty2, a Mouse Deafness Gene, Regulates Cell Fate Decisions in the Auditory Sensory Epithelium by Antagonizing FGF Signaling

Katherine Shim¹, George Minowada^1, 3, Donald E. Coling^2, 4 and Gail R. Martin^1, ,  

¹ Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California, San Francisco, San Francisco, California 94143
² Laboratory of Molecular Otology, Saul and Ida Epstein Laboratories, Department of Otolaryngology, University of California, San Francisco, San Francisco, California 94143

Ph: (415) 476-2441; Fax: (415) 476-3892

³ Present address: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Case Western Reserve University, School of Medicine, University Hospitals of Cleveland, Cleveland, Ohio 44106

⁴ Present address: Center for Hearing and Deafness, 137F Cary Hall (South Campus), The State University of New York at Buffalo, Buffalo, New York 14214

Summary

The auditory sensory epithelium (organ of Corti), where sound waves are converted to electrical signals, comprises a highly ordered array of sensory receptor (hair) cells and nonsensory supporting cells. Here, we report that Sprouty2, which encodes a negative regulator of signaling via receptor tyrosine kinases, is required for normal hearing in mice, and that lack of SPRY2 results in dramatic perturbations in organ of Corti cytoarchitecture: instead of two pillar cells, there are three, resulting in the formation of an ectopic tunnel of Corti. We demonstrate that these effects are due to a postnatal cell fate transformation of a Deiters’ cell into a pillar cell. Both this cell fate change and hearing loss can be partially rescued by reducing Fgf8 gene dosage in Spry2 null mutant mice. Our results provide evidence that antagonism of FGF signaling by SPRY2 is essential for establishing the cytoarchitecture of the organ of Corti and for hearing.