title: Tenascin-C is required for normal Wnt/β-catenin signaling in the whisker follicle stem cell niche.
abstract: 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.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.
authors.forename: Ismaïl
authors.initials: I
authors.lastname: Hendaoui
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California at Davis, Davis, CA, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Tucker
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Zingg
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bichet
authors.affiliation: Institute of Anatomy, University of Bern, Bern, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schittny
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland; Faculty of Science, University of Basel, Basel, Switzerland. Electronic address: ruth.chiquet@fmi.ch.
authors.forename: Ruth
authors.initials: R
authors.lastname: Chiquet-Ehrismann
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D018859:Hair Follicle / Q000166:cytology*; D006652:Histological Techniques; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D013234:Stem Cells / Q000502:physiology*; D019063:Tenascin / Q000235:genetics / Q000494:pharmacology*; D014738:Vibrissae / Q000166:cytology*; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D019063:Tenascin; D051176:beta Catenin
keywords: Stem cell niche; Tenascin; Vibrissa; Whisker; Wnt; beta-Catenin