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Sox2 in the differentiation of cochlear progenitor cells

HMG domain transcription factor, Sox2, is a critical gene for the development of cochlear hair cells, the receptor cells for hearing, but this has been ascribed to expansion of the progenitors that become hair cells. Here, we show that Sox2 activated Atoh1, a transcription factor important for hair...

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Autores principales: Kempfle, Judith S., Turban, Jack L., Edge, Albert S. B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796895/
https://www.ncbi.nlm.nih.gov/pubmed/26988140
http://dx.doi.org/10.1038/srep23293
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author Kempfle, Judith S.
Turban, Jack L.
Edge, Albert S. B.
author_facet Kempfle, Judith S.
Turban, Jack L.
Edge, Albert S. B.
author_sort Kempfle, Judith S.
collection PubMed
description HMG domain transcription factor, Sox2, is a critical gene for the development of cochlear hair cells, the receptor cells for hearing, but this has been ascribed to expansion of the progenitors that become hair cells. Here, we show that Sox2 activated Atoh1, a transcription factor important for hair cell differentiation, through an interaction with the 3′ enhancer of Atoh1. Binding to consensus sequences in the Atoh1 enhancer was dependent on the level of Sox2, and the extent of enhancer binding correlated to the extent of activation. Atoh1 activation by Sox2 was required for embryonic hair cell development: deletion of Sox2 in an inducible mutant, even after progenitor cells were fully established, halted development of hair cells, and silencing also inhibited postnatal differentiation of hair cells induced by inhibition of γ-secretase. Sox2 is thus required in the cochlea to both expand the progenitor cells and initiate their differentiation to hair cells.
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spelling pubmed-47968952016-03-21 Sox2 in the differentiation of cochlear progenitor cells Kempfle, Judith S. Turban, Jack L. Edge, Albert S. B. Sci Rep Article HMG domain transcription factor, Sox2, is a critical gene for the development of cochlear hair cells, the receptor cells for hearing, but this has been ascribed to expansion of the progenitors that become hair cells. Here, we show that Sox2 activated Atoh1, a transcription factor important for hair cell differentiation, through an interaction with the 3′ enhancer of Atoh1. Binding to consensus sequences in the Atoh1 enhancer was dependent on the level of Sox2, and the extent of enhancer binding correlated to the extent of activation. Atoh1 activation by Sox2 was required for embryonic hair cell development: deletion of Sox2 in an inducible mutant, even after progenitor cells were fully established, halted development of hair cells, and silencing also inhibited postnatal differentiation of hair cells induced by inhibition of γ-secretase. Sox2 is thus required in the cochlea to both expand the progenitor cells and initiate their differentiation to hair cells. Nature Publishing Group 2016-03-18 /pmc/articles/PMC4796895/ /pubmed/26988140 http://dx.doi.org/10.1038/srep23293 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kempfle, Judith S.
Turban, Jack L.
Edge, Albert S. B.
Sox2 in the differentiation of cochlear progenitor cells
title Sox2 in the differentiation of cochlear progenitor cells
title_full Sox2 in the differentiation of cochlear progenitor cells
title_fullStr Sox2 in the differentiation of cochlear progenitor cells
title_full_unstemmed Sox2 in the differentiation of cochlear progenitor cells
title_short Sox2 in the differentiation of cochlear progenitor cells
title_sort sox2 in the differentiation of cochlear progenitor cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796895/
https://www.ncbi.nlm.nih.gov/pubmed/26988140
http://dx.doi.org/10.1038/srep23293
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