The Journal of Neuroscience, June 4, 2008, 28(23):5991-5999; doi:10.1523/JNEUROSCI.1690-08.2008
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Development/Plasticity/Repair
Fgf20 Is Required for Sensory Epithelial Specification in the Developing Cochlea
Toshinori Hayashi,1,2
Catherine A. Ray,2 and
Olivia Bermingham-McDonogh1,2
1Virginia Merrill Bloedel Hearing Research Center and 2Department of Biological Structure, University of Washington, Seattle, Washington 98195
Correspondence should be addressed to Dr. Olivia Bermingham-McDonogh, Department of Biological Structure, Box 357920, University of Washington, Seattle, WA 98195. Email: oliviab{at}u.washington.edu
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.
Key words: hair cell; support cell; inner ear; sensory development; auditory; hearing
Received Feb. 19, 2008;
accepted May 1, 2008.
Correspondence should be addressed to Dr. Olivia Bermingham-McDonogh, Department of Biological Structure, Box 357920, University of Washington, Seattle, WA 98195. Email: oliviab{at}u.washington.edu
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S. L. Mansour, S. R.F. Twigg, R. M. Freeland, S. A. Wall, C. Li, and A. O.M. Wilkie
Hearing loss in a mouse model of Muenke syndrome
Hum. Mol. Genet.,
January 1, 2009;
18(1):
43 - 50.
[Abstract]
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