Hendaoui, Ismaïl; Tucker, Richard P; Zingg, Dominik; Bichet, Sandrine; Schittny, Johannes; Chiquet-Ehrismann, Ruth (2014). Tenascin-C is required for normal Wnt/β-catenin signaling in the whisker follicle stem cell niche. Matrix biology, 40, pp. 46-53. Elsevier 10.1016/j.matbio.2014.08.017
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Whisker follicles have multiple stem cell niches, including epidermal stem cells in the bulge as well as neural crest-derived stem cells and mast cell progenitors in the trabecular region. The neural crest-derived stem cells are a pool of melanocyte precursors. Previously, we found that the extracellular matrix glycoproteins tenascin-C and tenascin-W are expressed near CD34-positive cells in the trabecular stem cell niche of mouse whisker follicles. Here, we analyzed whiskers from tenascin-C knockout mice and found intrafollicular adipocytes and supernumerary mast cells. As Wnt/β-catenin signaling promotes melanogenesis and suppresses the differentiation of adipocytes and mast cells, we analyzed β-catenin subcellular localization in the trabecular niche. We found cytoplasmic and nuclear β-catenin in wild-type mice reflecting active Wnt/β-catenin signaling, whereas β-catenin in tenascin-C knockout mice was mostly cell membrane-associated and thus transcriptionally inactive. Furthermore, cells expressing the Wnt/β-catenin target gene cyclin D1 were enriched in the CD34-positive niches of wild-type compared to tenascin-C knockout mice. We then tested the effects of tenascins on this signaling pathway. We found that tenascin-C and tenascin-W can be co-precipitated with Wnt3a. In vitro, substrate bound tenascins promoted β-catenin-mediated transcription in the presence of Wnt3a, presumably due to the sequestration and concentration of Wnt3a near the cell surface. We conclude that the presence of tenascin-C in whiskers assures active Wnt/β-catenin signaling in the niche thereby maintaining the stem cell pool and suppressing aberrant differentiation, while in the knockout mice with reduced Wnt/β-catenin signaling, stem cells from the trabecular niche can differentiate into ectopic adipocytes and mast cells.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy |
UniBE Contributor: |
Schittny, Johannes |
Subjects: |
500 Science > 570 Life sciences; biology |
ISSN: |
0945-053X |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Johannes Schittny |
Date Deposited: |
27 Jan 2015 11:28 |
Last Modified: |
05 Dec 2022 14:39 |
Publisher DOI: |
10.1016/j.matbio.2014.08.017 |
PubMed ID: |
25196097 |
Uncontrolled Keywords: |
Stem cell niche, Tenascin, Vibrissa, Whisker, Wnt, beta-Catenin |
BORIS DOI: |
10.7892/boris.62146 |
URI: |
https://boris.unibe.ch/id/eprint/62146 |
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