Disruption of Fibroblast Growth Factor Receptor 3 Signaling Results in Defects in Cellular Differentiation, Neuronal Patterning, and Hearing Impairment

Chandrakala Puligilla; Feng Feng; Kotaro Ishikawa; Stefano Bertuzzi; Alain Dabdoub; Andrew J Griffith; Bernd Fritzsch; Matthew W Kelley

doi:10.1002/dvdy.21192

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Disruption of Fibroblast Growth Factor Receptor 3 Signaling Results in Defects in Cellular Differentiation, Neuronal Patterning, and Hearing Impairment

Journal article

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Disruption of Fibroblast Growth Factor Receptor 3 Signaling Results in Defects in Cellular Differentiation, Neuronal Patterning, and Hearing Impairment

Chandrakala Puligilla, Feng Feng, Kotaro Ishikawa, Stefano Bertuzzi, Alain Dabdoub, Andrew J Griffith, Bernd Fritzsch and Matthew W Kelley

Developmental dynamics, Vol.236(7), pp.1905-1917

07/2007

DOI: 10.1002/dvdy.21192

PMCID: PMC3904742

PMID: 17557302

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https://www.ncbi.nlm.nih.gov/pmc/articles/3904742View

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Abstract

Deletion of\nfibroblast growth factor receptor 3 (Fgfr3)\nleads to hearing impairment in mice due to defects in the development of the organ of Corti, the sensory epithelium of the Cochlea. To examine the role of FGFR3 in auditory development, cochleae from\nFgfr3\n−\n/\n−\nmice were examined using anatomical and physiological methods. Deletion of\nFgfr3\nleads to the absence of inner pillar cells and an increase in other cell types, suggesting that FGFR3 regulates cell fate. Defects in outer hair cell differentiation were also observed and probably represent the primary basis for hearing loss. Furthermore, innervation defects were detected consistent with changes in the fiber guidance properties of pillar cells. To elucidate the mechanisms underlying the effects of FGFR3, we examined the expression of\nBmp4\n, a known target.\nBmp4\nwas increased in\nFgfr3\n−\n/\n−\ncochleae, and exogenous application of bone morphogenetic protein 4 (BMP4) onto cochlear explants induced a significant increase in the outer hair cells, suggesting the Fgf and Bmp signaling act in concert to pattern the cochlea.

BMP4

cochlea

Deiters’ cells

hair cell

Prox1

Pillar cells

microtubules

innervation

stria vascularis

Details

Title: Subtitle: Disruption of Fibroblast Growth Factor Receptor 3 Signaling Results in Defects in Cellular Differentiation, Neuronal Patterning, and Hearing Impairment
Creators: Chandrakala Puligilla - Section on Developmental Neuroscience, NIDCD/NIH, Bethesda, Maryland
Feng Feng - Department of Biomedical Sciences, Creighton University, Omaha, Nebraska
Kotaro Ishikawa - Otolaryngology Branch, NIDCD/NIH, Rockville, Maryland
Stefano Bertuzzi - Mammalian Development Section, NINDS/NIH, Bethesda, Maryland
Alain Dabdoub - Section on Developmental Neuroscience, NIDCD/NIH, Bethesda, Maryland
Andrew J Griffith - Otolaryngology Branch, NIDCD/NIH, Rockville, Maryland
Bernd Fritzsch - Department of Biomedical Sciences, Creighton University, Omaha, Nebraska
Matthew W Kelley - Section on Developmental Neuroscience, NIDCD/NIH, Bethesda, Maryland
Resource Type: Journal article
Publication Details: Developmental dynamics, Vol.236(7), pp.1905-1917
DOI: 10.1002/dvdy.21192
PMID: 17557302
PMCID: PMC3904742
NLM abbreviation: Dev Dyn
ISSN: 1058-8388
eISSN: 1097-0177
Grant note: R01 DC005590-01 || DC / National Institute on Deafness and Other Communication Disorders : NIDCD
Language: English
Date published: 07/2007
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984070301302771

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