FGFR1-Frs2/3 signalling maintains sensory progenitors during inner ear hair cell formation.
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.
Sensory Development, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan ; Neurogenesis and Organogenesis, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan.
Kazuya
K
Ono
Sensory Development, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan.
Tomoko
T
Kita
Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Shigeru
S
Sato
Sensory Development, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan.
Paul
P
O'Neill
Sensory Development, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan.
Siu-Shan
SS
Mak
Sensory Development, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan.
Marie
M
Paschaki
Department of Anatomy, National Defense Medical College, Tokorozawa, Japan.
Masataka
M
Ito
Division of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
Noriko
N
Gotoh
Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Kiyoshi
K
Kawakami
Neurogenesis and Organogenesis, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan.
Yoshiki
Y
Sasai
Sensory Development, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan.
Raj K
RK
Ladher
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation / Q000235:genetics; D003051:Cochlea / Q000254:growth & development / Q000378:metabolism; D007758:Ear, Inner / Q000166:cytology / Q000254:growth & development*; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006199:Hair Cells, Auditory, Inner / Q000166:cytology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C488187:FRS2alpha protein, mouse; C485162:Frs3 protein, mouse; D008565:Membrane Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1