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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-98816-w |
| _version_ | 1818347484180643840 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T17:34:53Z |
| format | Article |
| id | doaj.art-6207ae42d90345088380c5f50a660313 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T17:34:53Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6207ae42d90345088380c5f50a6603132022-12-21T23:36:57ZengNature PortfolioScientific Reports2045-23222021-09-0111111310.1038/s41598-021-98816-wDifferential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner earMiriam Gómez-Dorado0Nicolas Daudet1Jonathan E. Gale2Sally J. Dawson3UCL Ear InstituteUCL Ear InstituteUCL Ear InstituteUCL Ear InstituteAbstract 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.https://doi.org/10.1038/s41598-021-98816-w |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-98816-w |
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