ArticleProceedings of the National Academy of Sciences of the United States of America2021
R-spondin substitutes for neuronal input for taste cell regeneration in adult mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Establishment of a Three-Dimensional In Vitro Model of Taste Bud Cells for Fat Taste Investigation.International journal of molecular sciences · 2026Article
- Converging Signaling Networks Drive Taste Bud Morphogenesis, Turnover, and Regeneration.International journal of molecular sciences · 2026Review
- Expression ofbioRxiv : the preprint server for biology · 2026Article
- Tamoxifen triggers a transcriptional switch from proliferation to differentiation in the circumvallate taste epithelium in mice.Scientific reports · 2025Article
- c-Kit signaling confers damage-resistance to sweet taste cells upon nerve injury.International journal of oral science · 2025Article
- Gustatory-neuron-supplied R-spondin-2 is required for taste bud replenishment.Stem cell reports · 2025Article
- Organoid models for chemosensing cell studies.American journal of physiology. Cell physiology · 2025Review
- Article
- Developing and regenerating a sense of taste.Current topics in developmental biology · 2025Review
- Organoids in the oral and maxillofacial region: present and future.International journal of oral science · 2024Review
- Reassessing the genetic lineage tracing of lingualAnimal cells and systems · 2024Article
- Cyclophosphamide induces the loss of taste bud innervation in mice.Chemical senses · 2024Article
- Give-and-take of gustation: the interplay between gustatory neurons and taste buds.Chemical senses · 2024Review
- Ascl1-expressing cell differentiation in initially developed taste buds and taste organoids.Cell and tissue research · 2023Article
- EGR4 is critical for cell-fate determination and phenotypic maintenance of geniculate ganglion neurons underlying sweet and umami taste.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Interleukin (IL)-1 Receptor Signaling Is Required for Complete Taste Bud Regeneration and the Recovery of Neural Taste Responses following Axotomy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Early Steps towards Hearing: Placodes and Sensory Development.International journal of molecular sciences · 2023Review
- Physiology of the tongue with emphasis on taste transduction.Physiological reviews · 2023Review
- Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis.Blood advances · 2023Article
- The biological functions and related signaling pathways of SPON2.Frontiers in oncology · 2023Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Taste bud cells regenerate throughout life. Taste bud maintenance depends on continuous replacement of senescent taste cells with new ones generated by adult taste stem cells. More than a century ago it was shown that taste buds degenerate after their innervating nerves are transected and that they are not restored until after reinnervation by distant gustatory ganglion neurons. Thus, neuronal input, likely via neuron-supplied factors, is required for generation of differentiated taste cells and taste bud maintenance. However, the identity of such a neuron-supplied niche factor(s) remains unclear. Here, by mining a published RNA-sequencing dataset of geniculate ganglion neurons and by in situ hybridization, we demonstrate that R-spondin-2, the ligand of Lgr5 and its homologs Lgr4/6 and stem-cell-expressed E3 ligases Rnf43/Znrf3, is expressed in nodose-petrosal and geniculate ganglion neurons. Using the glossopharyngeal nerve transection model, we show that systemic delivery of R-spondin via adenovirus can promote generation of differentiated taste cells despite denervation. Thus, exogenous R-spondin can substitute for neuronal input for taste bud cell replenishment and taste bud maintenance. Using taste organoid cultures, we show that R-spondin is required for generation of differentiated taste cells and that, in the absence of R-spondin in culture medium, taste bud cells are not generated ex vivo. Thus, we propose that R-spondin-2 may be the long-sought neuronal factor that acts on taste stem cells for maintaining taste tissue homeostasis.
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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.