FGFR1 Is Required for the Development of the Auditory Sensory Epithelium

The mammalian auditory sensory epithelium, the organ of Corti, comprises the hair cells and supporting cells that are pivotal for hearing function. The origin and development of their precursors are poorly understood. Here we show that loss-of-function mutations in mouse fibroblast growth factor rec...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2002-08, Vol.35 (4), p.671-680
Main Authors: Pirvola, Ulla, Ylikoski, Jukka, Trokovic, Ras, Hébert, Jean M, McConnell, Susan K, Partanen, Juha
Format: Article
Language:English
Subjects:
Animals
Basic Helix-Loop-Helix Transcription Factors
Calbindins
Cell Communication - genetics
Cell cycle
Cell Death - genetics
Cell Differentiation - genetics
Cell Division - genetics
Cyclin-dependent kinases
DNA-Binding Proteins - genetics
Ears & hearing
Female
Fetus
Fibroblast Growth Factor 2 - metabolism
Forkhead Transcription Factors
Gene Dosage
Gene Expression Regulation, Developmental - physiology
Hair Cells, Auditory - abnormalities
Hair Cells, Auditory - metabolism
Hair Cells, Auditory - ultrastructure
Integrases - genetics
Kinases
Male
Mice
Mice, Mutant Strains
Morphogenesis
Mutation
Mutation - genetics
Nerve Tissue Proteins - genetics
Protein Isoforms - genetics
Receptor Protein-Tyrosine Kinases - deficiency
Receptor Protein-Tyrosine Kinases - genetics
Receptor, Fibroblast Growth Factor, Type 1
Receptors, Fibroblast Growth Factor - deficiency
Receptors, Fibroblast Growth Factor - genetics
RNA, Messenger - metabolism
Rodents
S100 Calcium Binding Protein G - metabolism
Signal Transduction - genetics
Stem Cells - metabolism
Stem Cells - ultrastructure
Transcription Factors - metabolism
Viral Proteins - genetics
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Summary:The mammalian auditory sensory epithelium, the organ of Corti, comprises the hair cells and supporting cells that are pivotal for hearing function. The origin and development of their precursors are poorly understood. Here we show that loss-of-function mutations in mouse fibroblast growth factor receptor 1 ( Fgfr1) cause a dose-dependent disruption of the organ of Corti. Full inactivation of Fgfr1 in the inner ear epithelium by Foxg1-Cre-mediated deletion leads to an 85% reduction in the number of auditory hair cells. The primary cause appears to be reduced precursor cell proliferation in the early cochlear duct. Thus, during development, FGFR1 is required for the generation of the precursor pool, which gives rise to the auditory sensory epithelium. Our data also suggest that FGFR1 might have a distinct later role in intercellular signaling within the differentiating auditory sensory epithelium.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(02)00824-3