Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear
| Autor: | Sally J. Dawson, Jonathan E. Gale, Miriam Gómez-Dorado, Nicolas Daudet |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
ATOH1
Cell biology Molecular biology Science Chick Embryo Article Cell Line 03 medical and health sciences Mice 0302 clinical medicine Hair Cells Auditory medicine Basic Helix-Loop-Helix Transcription Factors E2F1 Animals Regeneration Inner ear E2F Transcription factor 030304 developmental biology 0303 health sciences Multidisciplinary biology Regeneration (biology) E2F Transcription Factor Family medicine.anatomical_structure Gene Expression Regulation biology.protein Medicine Auditory system Hair cell sense organs 030217 neurology & neurosurgery E2F1 Transcription Factor Neuroscience |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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