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MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells

MAP3K1 is a serine/threonine kinase that is activated by a diverse set of stimuli and exerts its effect through various downstream effecter molecules, including JNK, ERK1/2 and p38. In humans, mutant alleles of MAP3K1 are associated with 46,XY sex reversal. Until recently, the only phenotype observe...

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Autores principales: Yousaf, Rizwan, Meng, Qinghang, Hufnagel, Robert B., Xia, Ying, Puligilla, Chandrakala, Ahmed, Zubair M., Riazuddin, Saima
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728323/
https://www.ncbi.nlm.nih.gov/pubmed/26496772
http://dx.doi.org/10.1242/dmm.023077
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author Yousaf, Rizwan
Meng, Qinghang
Hufnagel, Robert B.
Xia, Ying
Puligilla, Chandrakala
Ahmed, Zubair M.
Riazuddin, Saima
author_facet Yousaf, Rizwan
Meng, Qinghang
Hufnagel, Robert B.
Xia, Ying
Puligilla, Chandrakala
Ahmed, Zubair M.
Riazuddin, Saima
author_sort Yousaf, Rizwan
collection PubMed
description MAP3K1 is a serine/threonine kinase that is activated by a diverse set of stimuli and exerts its effect through various downstream effecter molecules, including JNK, ERK1/2 and p38. In humans, mutant alleles of MAP3K1 are associated with 46,XY sex reversal. Until recently, the only phenotype observed in Map3k1(tm1Yxia) mutant mice was open eyelids at birth. Here, we report that homozygous Map3k1(tm1Yxia) mice have early-onset profound hearing loss accompanied by the progressive degeneration of cochlear outer hair cells. In the mouse inner ear, MAP3K1 has punctate localization at the apical surface of the supporting cells in close proximity to basal bodies. Although the cytoarchitecture, neuronal wiring and synaptic junctions in the organ of Corti are grossly preserved, Map3k1(tm1Yxia) mutant mice have supernumerary functional outer hair cells (OHCs) and Deiters' cells. Loss of MAP3K1 function resulted in the downregulation of Fgfr3, Fgf8, Fgf10 and Atf3 expression in the inner ear. Fgfr3, Fgf8 and Fgf10 have a role in induction of the otic placode or in otic epithelium development in mice, and their functional deficits cause defects in cochlear morphogenesis and hearing loss. Our studies suggest that MAP3K1 has an essential role in the regulation of these key cochlear morphogenesis genes. Collectively, our data highlight the crucial role of MAP3K1 in the development and function of the mouse inner ear and hearing.
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spelling pubmed-47283232016-02-01 MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells Yousaf, Rizwan Meng, Qinghang Hufnagel, Robert B. Xia, Ying Puligilla, Chandrakala Ahmed, Zubair M. Riazuddin, Saima Dis Model Mech Research Article MAP3K1 is a serine/threonine kinase that is activated by a diverse set of stimuli and exerts its effect through various downstream effecter molecules, including JNK, ERK1/2 and p38. In humans, mutant alleles of MAP3K1 are associated with 46,XY sex reversal. Until recently, the only phenotype observed in Map3k1(tm1Yxia) mutant mice was open eyelids at birth. Here, we report that homozygous Map3k1(tm1Yxia) mice have early-onset profound hearing loss accompanied by the progressive degeneration of cochlear outer hair cells. In the mouse inner ear, MAP3K1 has punctate localization at the apical surface of the supporting cells in close proximity to basal bodies. Although the cytoarchitecture, neuronal wiring and synaptic junctions in the organ of Corti are grossly preserved, Map3k1(tm1Yxia) mutant mice have supernumerary functional outer hair cells (OHCs) and Deiters' cells. Loss of MAP3K1 function resulted in the downregulation of Fgfr3, Fgf8, Fgf10 and Atf3 expression in the inner ear. Fgfr3, Fgf8 and Fgf10 have a role in induction of the otic placode or in otic epithelium development in mice, and their functional deficits cause defects in cochlear morphogenesis and hearing loss. Our studies suggest that MAP3K1 has an essential role in the regulation of these key cochlear morphogenesis genes. Collectively, our data highlight the crucial role of MAP3K1 in the development and function of the mouse inner ear and hearing. The Company of Biologists 2015-12-01 /pmc/articles/PMC4728323/ /pubmed/26496772 http://dx.doi.org/10.1242/dmm.023077 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Yousaf, Rizwan
Meng, Qinghang
Hufnagel, Robert B.
Xia, Ying
Puligilla, Chandrakala
Ahmed, Zubair M.
Riazuddin, Saima
MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells
title MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells
title_full MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells
title_fullStr MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells
title_full_unstemmed MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells
title_short MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells
title_sort map3k1 function is essential for cytoarchitecture of the mouse organ of corti and survival of auditory hair cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728323/
https://www.ncbi.nlm.nih.gov/pubmed/26496772
http://dx.doi.org/10.1242/dmm.023077
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