Fgf20 is required for sensory epithelial specification in the developing cochlea.
Tissue-specific deletion of Fgfr1 results in severe defects in the development of both hair cells and support cells (Pirvola et al., 2002). Despite the importance of Fgfr1 in this early phase of cochlear development, the timing for the requirement for FGF signaling at this stage is not known. Therefore, we investigated the requirement for FGF signaling at early stages of cochlear development using an FGF receptor inhibitor. We find that inhibition of FGF signaling from embryonic day 14 (E14) to E16 has a dramatic effect on the development of the sensory epithelium, causing a severe reduction in hair cells and support cells, similar to that reported for the Fgfr1 deletion. The effects of inhibition of FGF signaling on sensory specification are not explained by increases in cell death or changes in proliferation but lead to a rapid reduction in Pea3 and Erm and a loss of Math1 expression. We also show that a specific FGF, FGF20, is the likely ligand for FGFR1 at this sensory specification phase of cochlear development; Fgf20 is expressed at the right time and place to mediate sensory cell specification, and blocking FGF20 with a specific antibody inhibits hair cell and support cell development in a manner similar to the FGF receptor inhibitor. Our results thus define the period of FGF-dependent sensory cell specification and the ligand that mediates this step in cochlear development.
Virginia Merrill Bloedel Hearing Research Center and Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA.
Toshinori
T
Hayashi
Catherine A
CA
Ray
Olivia
O
Bermingham-McDonogh
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D003051:Cochlea / Q000196:embryology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000378:metabolism*; D051379:Mice; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D011758:Pyrroles / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
C498812:Fgf20 protein, mouse; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; C105686:SU 5402; D005346:Fibroblast Growth Factors