ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Mature mice lacking Rbl2/p130 gene have supernumerary inner ear hair cells and supporting cells.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Biological insights from multi-omic analysis of 31 genomic risk loci for adult hearing difficulty.PLoS genetics · 2020Pooled it
- Design and Synthesis of New Quinoxaline Analogs to Regenerate Sensory Auditory Hair Cells.Cells · 2025Article
- AAV-regulatedMolecular therapy. Nucleic acids · 2024Article
- The Dual Roles of Triiodothyronine in Regulating the Morphology of Hair Cells and Supporting Cells during Critical Periods of Mouse Cochlear Development.International journal of molecular sciences · 2023Article
- Spatiotemporally controlled overexpression of cyclin D1 triggers generation of supernumerary cells in the postnatal mouse inner ear.Hearing research · 2020Article
- A mouse model of miR-96, miR-182 and miR-183 misexpression implicates miRNAs in cochlear cell fate and homeostasis.Scientific reports · 2018Article
- Cell-Specific Transcriptome Analysis Shows That Adult Pillar and Deiters' Cells Express Genes Encoding Machinery for Specializations of Cochlear Hair Cells.Frontiers in molecular neuroscience · 2018Article
- Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration.BMC neuroscience · 2017Article
- Development and regeneration of vestibular hair cells in mammals.Seminars in cell & developmental biology · 2017Review
- Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea.Frontiers of medicine · 2016Review
- Where hearing starts: the development of the mammalian cochlea.Journal of anatomy · 2016Review
- Generation of a Retinoblastoma (Rb)1-inducible dominant-negative (DN) mouse model.Frontiers in cellular neuroscience · 2015Article
- Opportunities and limits of the one gene approach: the ability of Atoh1 to differentiate and maintain hair cells depends on the molecular context.Frontiers in cellular neuroscience · 2015Review
- Inner ear supporting cells: rethinking the silent majority.Seminars in cell & developmental biology · 2013Review
- A historical to present-day account of efforts to answer the question: "what puts the brakes on mammalian hair cell regeneration?".Hearing research · 2013Review
- Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration.Hearing research · 2013Review
- Correct timing of proliferation and differentiation is necessary for normal inner ear development and auditory hair cell viability.Developmental dynamics : an official publication of the American Association of Anatomists · 2013Article
- The myc road to hearing restoration.Cells · 2012Article
- Conditional deletion of the human ortholog gene Dicer1 in Pax2-Cre expression domain impairs orofacial development.Indian journal of human genetics · 2012Article
- Understanding the evolution and development of neurosensory transcription factors of the ear to enhance therapeutic translation.Cell and tissue research · 2012Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Adult mammalian auditory hair cells (HCs) and their associated supporting cells (SCs) do not proliferate, and HC death leads to irreversible neurosensory hearing loss and balance impairment. In nonmammalian vertebrates, loss of HCs induces mitotic proliferation of adjacent nonsensory SCs and/or direct SC transdifferentiation to generate replacement cells. This results in the structural and functional recovery of the nonmammalian sensory systems. Potential replacement of mammalian auditory HCs, either by transplanting cells or by transforming existing cells through molecular therapy, has long been proposed. However, HC replacement strategies with clear therapeutic potential remain elusive. The retinoblastoma (pRB) family of cell cycle regulators, Rb1, Rbl1 (p107), and Rbl2 (p130), regulate the G(1)- to S-phase transition in proliferating cells. In the inner ear, the biochemical and molecular pathways involving pRBs, particularly p107 and p130, are relatively unexplored and their therapeutic suitability is yet to be determined. In this study, we analyzed the cochleae of adult p130 knock-out (p130(-/-)) mice and showed that lack of the p130 gene results in extra rows of HCs and SCs in the more apical regions of the cochlea. No evidence of transdifferentiation of these supernumerary SCs into HCs was observed in the p130(-/-) mouse. Nevertheless, unscheduled proliferation of SCs in the adult p130(-/-) cochlea coupled to downregulation of bona fide cell cycle inhibitors provides a mechanistic basis for the role of p130 as a regulator of SC and HC mitotic quiescence in the more apical regions of the cochlea. Interestingly, p130(-/-) mice exhibited nearly normal peripheral auditory sensitivity.
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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.