Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Calbindins
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Cell Communication / genetics*
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Cell Death / genetics
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Cell Differentiation / genetics*
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Cell Division / genetics*
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DNA-Binding Proteins / genetics
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Female
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Fetus
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Fibroblast Growth Factor 2 / metabolism
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Forkhead Transcription Factors
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Gene Dosage
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Gene Expression Regulation, Developmental / physiology
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Hair Cells, Auditory / abnormalities*
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Hair Cells, Auditory / metabolism
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Hair Cells, Auditory / ultrastructure
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Integrases / genetics
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Male
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Mice
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Mice, Mutant Strains
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Mutation / genetics*
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Nerve Tissue Proteins / genetics
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Protein Isoforms / genetics
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RNA, Messenger / metabolism
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Receptor Protein-Tyrosine Kinases / deficiency*
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor, Fibroblast Growth Factor, Type 1
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Receptors, Fibroblast Growth Factor / deficiency*
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Receptors, Fibroblast Growth Factor / genetics
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S100 Calcium Binding Protein G / metabolism
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Signal Transduction / genetics
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Stem Cells / metabolism*
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Stem Cells / ultrastructure
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Transcription Factors / metabolism
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Viral Proteins / genetics
Substances
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Atoh1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Calbindins
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DNA-Binding Proteins
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Forkhead Transcription Factors
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Foxd1 protein, mouse
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Nerve Tissue Proteins
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Protein Isoforms
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RNA, Messenger
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Receptors, Fibroblast Growth Factor
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S100 Calcium Binding Protein G
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Transcription Factors
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Viral Proteins
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Fibroblast Growth Factor 2
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Fgfr1 protein, mouse
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Cre recombinase
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Integrases