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| Main Authors: | , , , , , , , , , , |
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| Format: | Recurso digital |
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Zenodo
2025
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| Online Access: | https://doi.org/10.5281/zenodo.14531704 |
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Table of Contents:
- <p>Stem cell pluripotency gene <em>Sox2</em> stimulates expression of proneural basic-helix-loop-helix transcription factor <em>Atoh1</em>. <em>Sox2</em> is necessary for the development of cochlear hair cells and binds to the <em>Atoh1</em> 3' enhancer to stimulate <em>Atoh1</em> expression. We show here that <em>Sox2</em> deletion in late embryogenesis results in the formation of extra hair cells, in contrast to the absence of hair cell development obtained after <em>Sox2</em> knockout early in gestation. <em>Sox2</em> overexpression decreased the level of Atoh1 protein despite an increase in <em>Atoh1</em> mRNA. Sox2 upregulated E3 ubiquitin ligase, <em>Huwe1</em>, by direct binding to the <em>Huwe1</em> gene. By upregulating its cognate E3 ligase, <em>Sox2</em> disrupts the positive feedback loop through which Atoh1 protein increases the expression of <em>Atoh1</em>. We conclude that <em>Sox2</em> initiates expression, while also limiting continued activity of bHLH transcription factor, Atoh1, and this inhibition represents a new mechanism for regulating the activity of this powerful initiator of hair cell development.</p>