Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling.
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.
Shim
Katherine
K
Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California, San Francisco, California 94143, USA.
Minowada
George
G
Coling
Donald E
DE
Martin
Gail R
GR
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019070:Cell Lineage; D003638:Deafness / Q000235:genetics*; D004432:Ear, Middle / Q000033:anatomy & histology / Q000502:physiology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D006309:Hearing / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology; D009925:Organ of Corti / Q000002:abnormalities / Q000166:cytology* / Q000254:growth & development*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C496457:Fgf8 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse