RNF43/ZNRF3 negatively regulates taste tissue homeostasis and positively regulates dorsal lingual epithelial tissue homeostasis

Chanyi Lu, Xiaoli Lin, Jumpei Yamashita, Ranhui Xi, Minliang Zhou, Yali V Zhang, Hong Wang, Robert F Margolskee, Bon-Kyoung Koo, Hans Clevers, Ichiro Matsumoto, Peihua Jiang

Research output: Contribution to journal/periodicalArticleScientificpeer-review

3 Citations (Scopus)


Taste bud cells are renewed throughout life in a process requiring innervation. Recently, we reported that R-spondin substitutes for neuronal input for taste cell regeneration. R-spondin amplifies WNT signaling by interacting with stem-cell-expressed E3 ubiquitin ligases RNF43/ZNRF3 (negative regulators of WNT signaling) and G-protein-coupled receptors LGR4/5/6 (positive regulators of WNT signaling). Therefore, we hypothesized that RNF43/ZNRF3 may serve as a brake, controlled by gustatory neuron-produced R-spondin, for regulating taste tissue homeostasis. Here, we show that mice deficient for Rnf43/Znrf3 in KRT5-expressing epithelial stem/progenitor cells (RZ dKO) exhibited taste cell hyperplasia; in stark contrast, epithelial tissue on the tongue degenerated. WNT signaling blockade substantially reversed all these effects in RZ dKO mice. Furthermore, innervation becomes dispensable for taste cell renewal in RZ dKO mice. We thus demonstrate important but distinct functions of RNF43/ZNRF3 in regulating taste versus lingual epithelial tissue homeostasis.

Original languageEnglish
Pages (from-to)369-383
Number of pages15
JournalStem Cell Reports
Issue number2
Publication statusPublished - 08 Feb 2022


  • Animals
  • Benzeneacetamides/pharmacology
  • Epithelium/metabolism
  • Glossopharyngeal Nerve/surgery
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pyridines/pharmacology
  • Stem Cells/cytology
  • Taste/physiology
  • Taste Buds/metabolism
  • Tongue/cytology
  • Ubiquitin-Protein Ligases/deficiency
  • Wnt Signaling Pathway/drug effects


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