The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Hes1 is a negative regulator of inner ear hair cell differentiation
Abstract
Hair cell fate determination in the inner ear has been shown to be controlled by specific genes. Recent loss-of-function and gain-of-function experiments have demonstrated that Math1, a mouse homolog of the Drosophila gene atonal, is essential for the production of hair cells. To identify genes that may interact with Math1 and inhibit hair cell differentiation, we have focused on Hes1, a mammalian hairy and enhancer of split homolog, which is a negative regulator of neurogenesis. We report here that targeted deletion of Hes1 leads to formation of supernumerary hair cells in the cochlea and utricle of the inner ear. RT-PCR analysis shows that Hes1 is expressed in inner ear during hair cell differentiation and its expression is maintained in adulthood. In situ hybridization with late embryonic inner ear tissue reveals that Hes1 is expressed in supporting cells, but not hair cells, of the vestibular sensory epithelium. In the cochlea, Hes1 is selectively expressed in the greater epithelial ridge and lesser epithelial ridge regions which are adjacent to inner and outer hair cells. Co-transfection experiments in postnatal rat explant cultures show that overexpression of Hes1 prevents hair cell differentiation induced by Math1. Therefore Hes1 can negatively regulate hair cell differentiation by antagonizing Math1. These results suggest that a balance between Math1 and negative regulators such as Hes1 is crucial for the production of an appropriate number of inner ear hair cells.
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Cites
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Self-citationOverexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears
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Self-citationRegeneration of Sensory Hair Cells After Acoustic Trauma
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Cited by
van Es, J. H., van Gijn, M. E., Riccio, O., van den Born, M., Vooijs, M., Begthel, H., Cozijnsen, M., Robine, S., Winton, D. J., Radtke, F., et al. (2005) · Nature · doi:10.1038/nature03659 · Cited by 1,543
Math1 Gene Transfer Generates New Cochlear Hair Cells in Mature Guinea Pigs In Vivo
Kawamoto, K., Ishimoto, S.-I., Minoda, R., Brough, D. E., & Raphael, Y. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-11-04395.2003 · Cited by 438
Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear
Brooker, R., Hozumi, K., & Lewis, J. (2006) · Development · doi:10.1242/dev.02284 · Cited by 330
Zine, A., Aubert, A., Qiu, J., Therianos, S., Guillemot, F., Kageyama, R., & de Ribaupierre, F. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-13-04712.2001 · Cited by 294
Self-citationThe cochlear implant: historical aspects and future prospects
Eshraghi, A. A., Nazarian, R., Telischi, F. F., Rajguru, S. M., Truy, E., & Gupta, C. (2012) · The Anatomical Record · doi:10.1002/ar.22580 · Cited by 285
Metadata
- Authors
- Zheng, J. L., Shou, J., Guillemot, F., Kageyama, R., & Gao, W.-Q.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2000-11-01
- Volume
- 127
- Issue
- 21
- Pages
- 4551-4560
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2166509920
- Cited by
- 264
- References
- 50
- FWCI
- 6.66
- Type
- journal article
- Language
- en
- Open access
- closed
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