Gustatory-neuron-supplied R-spondin-2 is required for taste bud replenishment
Replenishment of taste cells in taste buds throughout life requires innervation. Recently, we provided evidence that R-spondin is sufficient to promote taste cell generation and restore taste buds in a nerve transection model. Yet, the necessity of gustatory-neuron-supplied R-spondin 2 (RSPO2) in taste tissue homeostasis has remained unresolved. We used genetic approaches to investigate this. In a strain that carries an Rspo2 hypomorphic allele, the number of taste buds was significantly reduced in these mice, compared to wild-type mice, in both anterior and posterior tongue. Specific ablation of Rspo2 in the nodose-petrosal-jugular ganglion complex in another mouse strain led to nearly complete loss of taste buds in the circumvallate papilla. Epithelial ablation of Rnf43/Znrf3, the activity of which is antagonized by R-spondin binding, led to exuberant, sustained expansion of taste buds. Thus, our data strongly support that the RSPO2-RNF43/ZNRF3 axis serves as a master regulator for taste tissue homeostasis.
Authors
- Keyan Luo
- Ranhui Xi (ORCID: https://orcid.org/0000-0003-2831-1348)
- Guillaume de Lartigue (ORCID: https://orcid.org/0000-0002-0032-8810)
- Myunghwan Choi (ORCID: https://orcid.org/0000-0002-4235-7003)
- Mingyue Han
- Minliang Zhou (ORCID: https://orcid.org/0000-0002-5657-8261)
- Kurt D. Hankenson (ORCID: https://orcid.org/0000-0001-6361-143X)
- Alan de Araujo (ORCID: https://orcid.org/0000-0003-2656-4077)
- Chanyi Lu (ORCID: https://orcid.org/0000-0002-6723-9345)
- Robert F. Margolskee (ORCID: https://orcid.org/0000-0002-9572-2887)
- Ichiro Matsumoto (ORCID: https://orcid.org/0000-0001-9987-7715)
- Peihua Jiang (ORCID: https://orcid.org/0000-0001-6705-8248)
- Xiaoli Lin (ORCID: https://orcid.org/0009-0009-1101-2465)
- Xu Jiang (ORCID: https://orcid.org/0000-0001-6405-9595)
Institutions
- Seoul National University (KR)
- University of Michigan (US)
- Monell Chemical Senses Center (US)
Publication Details
- Journal
- Stem Cell Reports
- Published
- 2025-06-19
- DOI
- https://doi.org/10.1016/j.stemcr.2025.102542
- Citations
- 1
- Primary Topic
- Biochemical Analysis and Sensing Techniques
- Type
- article
- Field-Weighted Citation Impact
- 1.12
Funders
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders