ArticleFrontiers in cellular neuroscience2016
LGR4 and LGR5 Regulate Hair Cell Differentiation in the Sensory Epithelium of the Developing Mouse Cochlea.
Article in Frontiers in cellular neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair.Human molecular genetics · 2018Pooled it
- Synergistic SHH activation and BMP inhibition remodel progenitor niche for enhanced hair cell generation.Science China. Life sciences · 2026Article
- Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea.Cells · 2025Article
- Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions.International journal of molecular sciences · 2023Review
- Article
- Long-term survival of LGR5 expressing supporting cells after severe ototoxic trauma in the adult mouse cochlea.Frontiers in cellular neuroscience · 2023Article
- G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss.Frontiers in molecular neuroscience · 2022Review
- The Role of LGR4 (GPR48) in Normal and Cancer Processes.International journal of molecular sciences · 2021Review
- LGR5-Positive Supporting Cells Survive Ototoxic Trauma in the Adult Mouse Cochlea.Frontiers in molecular neuroscience · 2021Article
- Hair Cell Generation in Cochlear Culture Models Mediated by Novel γ-Secretase Inhibitors.Frontiers in cell and developmental biology · 2021Article
- Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis.Frontiers in genetics · 2021Review
- Article
- Growth factor and receptor malfunctions associated with human genetic deafness.Clinical genetics · 2020Review
- Open chromatin dynamics in prosensory cells of the embryonic mouse cochlea.Scientific reports · 2019Article
- Therapeutic Potential of Wnt and Notch Signaling and Epigenetic Regulation in Mammalian Sensory Hair Cell Regeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Review
- Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea.Frontiers in molecular neuroscience · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the developing cochlea, Wnt/β-catenin signaling positively regulates the proliferation of precursors and promotes the formation of hair cells by up-regulating Atoh1 expression. Not much, however, is known about the regulation of Wnt/β-catenin activity in the cochlea. In multiple tissues, the activity of Wnt/β-catenin signaling is modulated by an interaction between LGR receptors and their ligands from the R-spondin family. The deficiency in Lgr4 and Lgr5 genes leads to developmental malformations and lethality. Using the Lgr5 knock-in mouse line we show that loss of LGR5 function increases Wnt/β-catenin activity in the embryonic cochlea, resulting in a mild overproduction of inner and outer hair cells (OHC). Supernumerary hair cells are likely formed due to an up-regulation of the "pro-hair cell" transcription factors Atoh1, Nhlh1, and Pou4f3. Using a hypomorphic Lgr4 mouse model we showed a mild overproduction of OHCs in the heterozygous and homozygous Lgr4 mice. The loss of LGR4 function prolonged the proliferation in the mid-basal turn of E13 cochleae, causing an increase in the number of SOX2-positive precursor cells within the pro-sensory domain. The premature differentiation of hair cells progressed in a medial to lateral gradient in Lgr4 deficient embryos. No significant up-regulation of Atoh1 was observed following Lgr4 deletion. Altogether, our findings suggest that LGR4 and LGR5 play an important role in the regulation of hair cell differentiation in the embryonic cochlea.
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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.