ArticleFrontiers in cellular neuroscience2015
Changes in the regulation of the Notch signaling pathway are temporally correlated with regenerative failure in the mouse cochlea.
Article in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 103 citations in OpenAlex.
- Synergistic SHH activation and BMP inhibition remodel progenitor niche for enhanced hair cell generation.Science China. Life sciences · 2026Article
- Evolutionary constraints impose multiple checkpoints that block mammalian sensory hair cell regeneration.Frontiers in cell and developmental biology · 2026Review
- The Notch ligand Jagged1 plays a dual role in cochlear hair cell regeneration.Nature communications · 2025Article
- AAV-Sparcl1 promotes hair cell regeneration by increasing supporting cell plasticity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Hearing restoration through hair cell regeneration: A review of recent advancements and current limitations.Hearing research · 2025Review
- Article
- Long-rangeProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Reprogramming withPNAS nexus · 2024Article
- Transdifferentiation is temporally uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear.Development (Cambridge, England) · 2024Article
- Article
- Transdifferentiation is uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear.bioRxiv : the preprint server for biology · 2024Article
- Expression ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Integrated scRNAseq analyses of mouse cochlear supporting cells reveal the involvement of Ezh2 in hair cell regeneration.Molecular biology reports · 2024Article
- SoxC transcription factors shape the epigenetic landscape to establish competence for sensory differentiation in the mammalian organ of Corti.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- DNA methylation in the mouse cochlea promotes maturation of supporting cells and contributes to the failure of hair cell regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- On the value of diverse organisms in auditory research: From fish to flies to humans.Hearing research · 2023Review
- Deletion ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- Deletion of the Notch ligand Jagged1 during cochlear maturation leads to inner hair cell defects and hearing loss.Cell death & disease · 2022Article
- The regenerative capacity of neonatal tissues.Development (Cambridge, England) · 2022Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Sensorineural hearing loss is most commonly caused by the death of hair cells in the organ of Corti, and once lost, mammalian hair cells do not regenerate. In contrast, other vertebrates such as birds can regenerate hair cells by stimulating division and differentiation of neighboring supporting cells. We currently know little of the genetic networks which become active in supporting cells when hair cells die and that are activated in experimental models of hair cell regeneration. Several studies have shown that neonatal mammalian cochlear supporting cells are able to trans-differentiate into hair cells when cultured in conditions in which the Notch signaling pathway is blocked. We now show that the ability of cochlear supporting cells to trans-differentiate declines precipitously after birth, such that supporting cells from six-day-old mouse cochlea are entirely unresponsive to a blockade of the Notch pathway. We show that this trend is seen regardless of whether the Notch pathway is blocked with gamma secretase inhibitors, or by antibodies against the Notch1 receptor, suggesting that the action of gamma secretase inhibitors on neonatal supporting cells is likely to be by inhibiting Notch receptor cleavage. The loss of responsiveness to inhibition of the Notch pathway in the first postnatal week is due in part to a down-regulation of Notch receptors and ligands, and we show that this down-regulation persists in the adult animal, even under conditions of noise damage. Our data suggest that the Notch pathway is used to establish the repeating pattern of hair cells and supporting cells in the organ of Corti, but is not required to maintain this cellular mosaic once the production of hair cells and supporting cells is completed. Our results have implications for the proposed used of Notch pathway inhibitors in hearing restoration therapies.
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