The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer
Open accessAbstract
Sensory hair cells in the mammalian cochlea convert mechanical stimuli into electrical impulses that subserve audition. Loss of hair cells and their innervating neurons is the most frequent cause of hearing impairment. Atonal homologue 1 (encoded by Atoh1, also known as Math1) is a basic helix–loop–helix transcription factor required for hair-cell development, and its misexpression in vitro and in vivo generates hair-cell-like cells. Atoh1-based gene therapy to ameliorate auditory and vestibular dysfunction has been proposed. However, the biophysical properties of putative hair cells induced by Atoh1 misexpression have not been characterized. Here we show that in utero gene transfer of Atoh1 produces functional supernumerary hair cells in the mouse cochlea. The induced hair cells display stereociliary bundles, attract neuronal processes and express the ribbon synapse marker carboxy-terminal binding protein 2 (refs 12,13). Moreover, the hair cells are capable of mechanoelectrical transduction and show basolateral conductances with age-appropriate specializations. Our results demonstrate that manipulation of cell fate by transcription factor misexpression produces functional sensory cells in the postnatal mammalian cochlea. We expect that our in utero gene transfer paradigm will enable the design and validation of gene therapies to ameliorate hearing loss in mouse models of human deafness.
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Cites
Math1 : An Essential Gene for the Generation of Inner Ear Hair Cells
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Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears
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Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals
Izumikawa, M., Minoda, R., Kawamoto, K., Abrashkin, K. A., Swiderski, D. L., Dolan, D. F., Brough, D. E., & Raphael, Y. (2005) · Nature Medicine · doi:10.1038/nm1193 · Cited by 741
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Unconventional Myosins in Inner-Ear Sensory Epithelia
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Math1 Gene Transfer Generates New Cochlear Hair Cells in Mature Guinea Pigs In Vivo
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Math1 regulates development of the sensory epithelium in the mammalian cochlea
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Graf, T., & Enver, T. (2009) · Nature · doi:10.1038/nature08533 · Cited by 899
Delivery of therapeutics to the inner ear: The challenge of the blood-labyrinth barrier
Nyberg, S., Abbott, N. J., Shi, X., Steyger, P. S., & Dabdoub, A. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aao0935 · Cited by 336
A quantitative morphological analysis of the inner ear of galliform birds
Corfield, J. R., Krilow, J. M., Vande Ligt, M. N., & Iwaniuk, A. N. (2013) · Hearing Research · doi:10.1016/j.heares.2013.07.004 · Cited by 17
Metadata
- Authors
- Gubbels, S. P., Woessner, D. W., Mitchell, J. C., Ricci, A. J., & Brigande, J. V.
- Venue
- Nature
- Published
- 2008-08-27
- Volume
- 455
- Issue
- 7212
- Pages
- 537-541
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2018514799
- Cited by
- 278
- References
- 29
- FWCI
- 10.43
- Type
- journal article
- Language
- en
- Open access
- green
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- Gubbels, S. P., Woessner, D. W., Mitchell, J. C., Ricci, A. J., & Brigande, J. V. (2008). Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer. Nature. https://doi.org/10.1038/nature07265
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