ArticleThe European journal of neuroscience2018
ERBB2 signaling drives supporting cell proliferation in vitro and apparent supernumerary hair cell formation in vivo in the neonatal mouse cochlea.
Article in The European journal of neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- In vitro evaluation of microfluidic WS6-loaded Eudragit nanoparticles for improving insulin-producing cell differentiation.PloS one · 2026Article
- Evolutionary constraints impose multiple checkpoints that block mammalian sensory hair cell regeneration.Frontiers in cell and developmental biology · 2026Review
- EPHRIN-A1 and -A2 act as positive growth factors for developing spiral ganglion radial bundles.Developmental biology · 2025Article
- The Reconstruction of Peripheral Auditory Circuit: Recent Advances and Future Challenges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Advance and Application of Single-cell Transcriptomics in Auditory Research.Neuroscience bulletin · 2024Review
- In silico transcriptome screens identify epidermal growth factor receptor inhibitors as therapeutics for noise-induced hearing loss.Science advances · 2024Article
- Modeling, applications and challenges of inner ear organoid.Smart medicine · 2024Review
- Reprogramming by drug-like molecules leads to regeneration of cochlear hair cell-like cells in adult mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Editorial: New insights in molecular pathways in ototoxicity.Frontiers in cellular neuroscience · 2023Article
- Article
- Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation.Frontiers in cellular neuroscience · 2022Article
- Development in the Mammalian Auditory System Depends on Transcription Factors.International journal of molecular sciences · 2021Review
- Neurog1, Neurod1, and Atoh1 are essential for spiral ganglia, cochlear nuclei, and cochlear hair cell development.Faculty reviews · 2021Review
- Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells.Frontiers in cellular neuroscience · 2021Article
- Perspectives on Human Hearing Loss, Cochlear Regeneration, and the Potential for Hearing Restoration Therapies.Brain sciences · 2020Review
- Using Sox2 to alleviate the hallmarks of age-related hearing loss.Ageing research reviews · 2020Review
- Inner ear organoids: new tools to understand neurosensory cell development, degeneration and regeneration.Development (Cambridge, England) · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
In mammals, cochlear hair cells are not regenerated once they are lost, leading to permanent hearing deficits. In other vertebrates, the adjacent supporting cells act as a stem cell compartment, in that they both proliferate and differentiate into de novo auditory hair cells. Although there is evidence that mammalian cochlear supporting cells can differentiate into new hair cells, the signals that regulate this process are poorly characterized. We hypothesize that signaling from the epidermal growth factor receptor (EGFR) family may play a role in cochlear regeneration. We focus on one such member, ERBB2, and report the effects of expressing a constitutively active ERBB2 receptor in neonatal mouse cochlear supporting cells, using viruses and transgenic expression. Lineage tracing with fluorescent reporter proteins was used to determine the relationships between cells with active ERBB2 signaling and cells that divided or differentiated into hair cells. In vitro, individual supporting cells harbouring a constitutively active ERBB2 receptor appeared to signal to their neighbouring supporting cells, inducing them to down-regulate a supporting cell marker and to proliferate. In vivo, we found supernumerary hair cell-like cells near supporting cells that expressed ERBB2 receptors. Both supporting cell proliferation and hair cell differentiation were largely reproduced in vitro using small molecules that we show also activate ERBB2. Our data suggest that signaling from the receptor tyrosine kinase ERBB2 can drive the activation of secondary signaling pathways to regulate regeneration, suggesting a new model where an interplay of cell signaling regulates regeneration by endogenous stem-like cells.
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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.