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 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.
Institute of Biotechnology, 00014 University of Helsinki, Helsinki, Finland. ulla.pirvola@helsinki.fi
Ulla
U
Pirvola
Jukka
J
Ylikoski
Ras
R
Trokovic
Jean M
JM
Hébert
Susan K
SK
McConnell
Juha
J
Partanen
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D064026:Calbindins; D002450:Cell Communication / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006198:Hair Cells, Auditory / Q000002:abnormalities* / Q000378:metabolism / Q000648:ultrastructure; D019426:Integrases / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency* / Q000235:genetics; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D064026:Calbindins; D004268:DNA-Binding Proteins; D016222:Fibroblast Growth Factor 2; D051858:Forkhead Transcription Factors; D019426:Integrases; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor; D064030:S100 Calcium Binding Protein G; D014157:Transcription Factors; D014764:Viral Proteins; C500943:Atoh1 protein, mouse; C489562:Foxd1 protein, mouse; C496349:Fgfr1 protein, mouse; C045073:Cre recombinase