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PMID:22235191

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Citation

Huh, SH, Jones, J, Warchol, ME and Ornitz, DM (2012) Differentiation of the lateral compartment of the cochlea requires a temporally restricted FGF20 signal. PLoS Biol. 10:e1001231

Abstract

A large proportion of age-related hearing loss is caused by loss or damage to outer hair cells in the organ of Corti. The organ of Corti is the mechanosensory transducing apparatus in the inner ear and is composed of inner hair cells, outer hair cells, and highly specialized supporting cells. The mechanisms that regulate differentiation of inner and outer hair cells are not known. Here we report that fibroblast growth factor 20 (FGF20) is required for differentiation of cells in the lateral cochlear compartment (outer hair and supporting cells) within the organ of Corti during a specific developmental time. In the absence of FGF20, mice are deaf and lateral compartment cells remain undifferentiated, postmitotic, and unresponsive to Notch-dependent lateral inhibition. These studies identify developmentally distinct medial (inner hair and supporting cells) and lateral compartments in the developing organ of Corti. The viability and hearing loss in Fgf20 knockout mice suggest that FGF20 may also be a deafness-associated gene in humans.

Links

PubMed PMC3250500 Online version:10.1371/journal.pbio.1001231

Keywords

Animals; Cell Differentiation/genetics; Cochlea/cytology; Cochlea/embryology; Cochlea/metabolism; Ear, Inner/cytology; Ear, Inner/embryology; Ear, Inner/metabolism; Female; Fibroblast Growth Factors/genetics; Fibroblast Growth Factors/metabolism; Gene Expression Regulation, Developmental; Hair Cells, Auditory/cytology; Hair Cells, Auditory/metabolism; Hearing Loss/genetics; Hearing Loss/metabolism; Humans; Immunohistochemistry; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Organ Culture Techniques; Organ of Corti/cytology; Organ of Corti/embryology; Organ of Corti/metabolism; Receptors, Notch/genetics; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FGF3

involved_in

GO:0030916: otic vesicle formation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FGFR1

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

  • occurs_in:(CL:0000601)

Seeded From UniProt

complete

MOUSE:FGFR1

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FGF8

involved_in

GO:0030916: otic vesicle formation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FGF8

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

  • has_input:(UniProtKB:P22607)

Seeded From UniProt

complete

MOUSE:FGFR3

involved_in

GO:0045597: positive regulation of cell differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

  • regulates_o_results_in_acquisition_of_features_of:(CL:1000191)

Seeded From UniProt

complete

MOUSE:FGF20

involved_in

GO:0045664: regulation of neuron differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_results_in_development_of:(CL:0000601)
  • occurs_in:(UBERON:0002227)

Seeded From UniProt

complete

MOUSE:FGF10

involved_in

GO:0030916: otic vesicle formation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FGF8

involved_in

GO:0045597: positive regulation of cell differentiation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

  • regulates_o_results_in_acquisition_of_features_of:(CL:0000202)
  • occurs_in:(CL:0000589)

Seeded From UniProt

complete

MOUSE:FGFR2

involved_in

GO:0030916: otic vesicle formation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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