Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear

Abstract The mammalian inner ear has a limited capacity to regenerate its mechanosensory hair cells. This lack of regenerative capacity underlies the high incidence of age-related hearing loss in humans. In contrast, non-mammalian vertebrates can form new hair cells when damage occurs, a mechanism t...

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Autores principales:	Miriam Gómez-Dorado, Nicolas Daudet, Jonathan E. Gale, Sally J. Dawson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6207ae42d90345088380c5f50a660313
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spelling	oai:doaj.org-article:6207ae42d90345088380c5f50a6603132021-12-02T17:37:41ZDifferential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear10.1038/s41598-021-98816-w2045-2322https://doaj.org/article/6207ae42d90345088380c5f50a6603132021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98816-whttps://doaj.org/toc/2045-2322Abstract The mammalian inner ear has a limited capacity to regenerate its mechanosensory hair cells. This lack of regenerative capacity underlies the high incidence of age-related hearing loss in humans. In contrast, non-mammalian vertebrates can form new hair cells when damage occurs, a mechanism that depends on re-activation of expression of the pro-hair cell transcription factor Atoh1. Here, we show that members of the E2F transcription factor family, known to play a key role in cell cycle progression, regulate the expression of Atoh1. E2F1 activates chicken Atoh1 by directly interacting with a cis-regulatory region distal to the avian Atoh1 gene. E2F does not activate mouse Atoh1 gene expression, since this regulatory element is absent in mammals. We also show that E2F1 expression changes dynamically in the chicken auditory epithelium during ototoxic damage and hair cell regeneration. Therefore, we propose a model in which the mitotic regeneration of non-mammalian hair cells is due to E2F1-mediated activation of Atoh1 expression, a mechanism which has been lost in mammals.Miriam Gómez-DoradoNicolas DaudetJonathan E. GaleSally J. DawsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Miriam Gómez-Dorado Nicolas Daudet Jonathan E. Gale Sally J. Dawson Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear
description	Abstract The mammalian inner ear has a limited capacity to regenerate its mechanosensory hair cells. This lack of regenerative capacity underlies the high incidence of age-related hearing loss in humans. In contrast, non-mammalian vertebrates can form new hair cells when damage occurs, a mechanism that depends on re-activation of expression of the pro-hair cell transcription factor Atoh1. Here, we show that members of the E2F transcription factor family, known to play a key role in cell cycle progression, regulate the expression of Atoh1. E2F1 activates chicken Atoh1 by directly interacting with a cis-regulatory region distal to the avian Atoh1 gene. E2F does not activate mouse Atoh1 gene expression, since this regulatory element is absent in mammals. We also show that E2F1 expression changes dynamically in the chicken auditory epithelium during ototoxic damage and hair cell regeneration. Therefore, we propose a model in which the mitotic regeneration of non-mammalian hair cells is due to E2F1-mediated activation of Atoh1 expression, a mechanism which has been lost in mammals.
format	article
author	Miriam Gómez-Dorado Nicolas Daudet Jonathan E. Gale Sally J. Dawson
author_facet	Miriam Gómez-Dorado Nicolas Daudet Jonathan E. Gale Sally J. Dawson
author_sort	Miriam Gómez-Dorado
title	Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear
title_short	Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear
title_full	Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear
title_fullStr	Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear
title_full_unstemmed	Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear
title_sort	differential regulation of mammalian and avian atoh1 by e2f1 and its implication for hair cell regeneration in the inner ear
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6207ae42d90345088380c5f50a660313
work_keys_str_mv	AT miriamgomezdorado differentialregulationofmammalianandavianatoh1bye2f1anditsimplicationforhaircellregenerationintheinnerear AT nicolasdaudet differentialregulationofmammalianandavianatoh1bye2f1anditsimplicationforhaircellregenerationintheinnerear AT jonathanegale differentialregulationofmammalianandavianatoh1bye2f1anditsimplicationforhaircellregenerationintheinnerear AT sallyjdawson differentialregulationofmammalianandavianatoh1bye2f1anditsimplicationforhaircellregenerationintheinnerear
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Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear

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