ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Auditory hair cell-specific deletion of p27Kip1 in postnatal mice promotes cell-autonomous generation of new hair cells and normal hearing.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Single-cell atlas comparison across vertebrates reveals auditory cell evolution and mechanisms for hair cell regeneration.Communications biology · 2024Article
- AAV-regulatedMolecular therapy. Nucleic acids · 2024Article
- Roles of supporting cells in the maintenance and regeneration of the damaged inner ear: A literature review.Journal of otology · 2024Review
- MEK/ERK signaling drives the transdifferentiation of supporting cells into functional hair cells by modulating the Notch pathway.Stem cells translational medicine · 2024Article
- Recent Therapeutic Progress and Future Perspectives for the Treatment of Hearing Loss.Biomedicines · 2023Review
- Gene therapy: an emerging therapy for hair cells regeneration in the cochlea.Frontiers in neuroscience · 2023Review
- Small Molecule Sequestration of the Intrinsically Disordered Protein, p27Journal of molecular biology · 2021Article
- Spatiotemporally controlled overexpression of cyclin D1 triggers generation of supernumerary cells in the postnatal mouse inner ear.Hearing research · 2020Article
- Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy.Frontiers in genetics · 2020Review
- Inner ear organoids: new tools to understand neurosensory cell development, degeneration and regeneration.Development (Cambridge, England) · 2019Review
- Approaches for the study of epigenetic modifications in the inner ear and related tissues.Hearing research · 2019Review
- Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies.Annals of the New York Academy of Sciences · 2019Review
- Article
- Neonatal mouse intervertebral discs heal with restored function following herniation injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- A Small Molecule Causes a Population Shift in the Conformational Landscape of an Intrinsically Disordered Protein.Journal of the American Chemical Society · 2017Article
- Development and regeneration of vestibular hair cells in mammals.Seminars in cell & developmental biology · 2017Review
- In Vivo Interplay between p27Cell reports · 2017Article
- Indispensable role of Mdm2/p53 interaction during the embryonic and postnatal inner ear development.Scientific reports · 2017Article
- Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea.Frontiers in molecular neuroscience · 2017Article
- Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea.Frontiers of medicine · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hearing in mammals relies upon the transduction of sound by hair cells (HCs) in the organ of Corti within the cochlea of the inner ear. Sensorineural hearing loss is a widespread and permanent disability due largely to a lack of HC regeneration in mammals. Recent studies suggest that targeting the retinoblastoma (Rb)/E2F pathway can elicit proliferation of auditory HCs. However, previous attempts to induce HC proliferation in this manner have resulted in abnormal cochlear morphology, HC death, and hearing loss. Here we show that cochlear HCs readily proliferate and survive following neonatal, HC-specific, conditional knock-out of p27(Kip1) (p27CKO), a tumor suppressor upstream of Rb. Indeed, HC-specific p27CKO results in proliferation of these cells without the upregulation of the supporting cell or progenitor cell proteins, Prox1 or Sox2, suggesting that they remain HCs. Furthermore, p27CKO leads to a significant addition of postnatally derived HCs that express characteristic synaptic and stereociliary markers and survive to adulthood, although a portion of the newly derived inner HCs exhibit cytocauds and lack VGlut3 expression. Despite this, p27CKO mice exhibit normal hearing as measured by evoked auditory brainstem responses, which suggests that the newly generated HCs may contribute to, or at least do not greatly detract from, function. These results show that p27(Kip1) actively maintains HC quiescence in postnatal mice, and suggest that inhibition of p27(Kip1) in residual HCs represents a potential strategy for cell-autonomous auditory HC regeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.