ArticleScientific reports2021
Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 18 citations in OpenAlex.
- Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq.BMC genomics · 2024Article
- Hair Cell Regeneration: From Animals to Humans.Clinical and experimental otorhinolaryngology · 2024Review
- Small activating RNA activation of ATOH1 promotes regeneration of human inner ear hair cells.Bioengineered · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
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.
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