FGFR1-Frs2/3 Signalling Maintains Sensory Progenitors during Inner Ear Hair Cell Formation
0303 health sciences
Hair Cells, Auditory, Inner
SOXB1 Transcription Factors
Cell Cycle
Gene Expression Regulation, Developmental
Membrane Proteins
Cell Differentiation
QH426-470
Epithelium
Cochlea
03 medical and health sciences
Ear, Inner
Genetics
Animals
Receptor, Fibroblast Growth Factor, Type 1
Research Article
Adaptor Proteins, Signal Transducing
Protein Binding
Signal Transduction
DOI:
10.1371/journal.pgen.1004118
Publication Date:
2014-01-23T23:13:08Z
AUTHORS (11)
ABSTRACT
Inner ear mechanosensory hair cells transduce sound and balance information. Auditory hair cells emerge from a Sox2-positive sensory patch in the inner ear epithelium, which is progressively restricted during development. This restriction depends on the action of signaling molecules. Fibroblast growth factor (FGF) signalling is important during sensory specification: attenuation of Fgfr1 disrupts cochlear hair cell formation; however, the underlying mechanisms remain unknown. Here we report that in the absence of FGFR1 signaling, the expression of Sox2 within the sensory patch is not maintained. Despite the down-regulation of the prosensory domain markers, p27(Kip1), Hey2, and Hes5, progenitors can still exit the cell cycle to form the zone of non-proliferating cells (ZNPC), however the number of cells that form sensory cells is reduced. Analysis of a mutant Fgfr1 allele, unable to bind to the adaptor protein, Frs2/3, indicates that Sox2 maintenance can be regulated by MAP kinase. We suggest that FGF signaling, through the activation of MAP kinase, is necessary for the maintenance of sensory progenitors and commits precursors to sensory cell differentiation in the mammalian cochlea.
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