RNF43/ZNRF3 negatively regulates taste tissue homeostasis and positively regulates dorsal lingual epithelial tissue homeostasis
Lu, Chanyi; Lin, Xiaoli; Yamashita, Jumpei; Xi, Ranhui; Zhou, Minliang; Zhang, Yali V.; Wang, Hong; Margolskee, Robert F.; Koo, Bon Kyoung; Clevers, Hans; Matsumoto, Ichiro; Jiang, Peihua
(2022) Stem Cell Reports, volume 17, issue 2, pp. 369 - 383
(Article)
Abstract
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
... read more
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.
show less
Download/Full Text
Keywords: LGR5, R-spondin, RNF43, taste stem cells, WNT, ZNRF3, Epithelium/metabolism, Mice, Inbred C57BL, Wnt Signaling Pathway/drug effects, Ubiquitin-Protein Ligases/deficiency, Mice, Knockout, Taste Buds/metabolism, Animals, Tongue/cytology, Mice, Benzeneacetamides/pharmacology, Taste/physiology, Stem Cells/cytology, Glossopharyngeal Nerve/surgery, Pyridines/pharmacology, Genetics, Biochemistry, Cell Biology, Developmental Biology, Journal Article, Research Support, N.I.H., Extramural
ISSN: 2213-6711
Publisher: Cell Press
Note: Funding Information: This work was supported by NIH grants DC010842 (to P.J.), DC018627 (to P.J.), DC015491 (to I.M.), and G20 OD020296 (to Danielle R. Reed). Imaging was performed at the Cell and Developmental Biology Core at the University of Pennsylvania and at the Monell Histology and Cellular Localization Core, which was supported in part by NIH National Institute on Deafness and Other Communication Disorders Core Grant DC011735 (to R.F.M.). The graphical abstract was created with BioRender.com . Publisher Copyright: © 2021 The Author(s)
(Peer reviewed)