Tenascin-C is required for normal Wnt/β-catenin signaling in the whisker follicle stem cell niche

Ismaïl Hendaoui, Richard P Tucker, Dominik Zingg, Sandrine Bichet, Johannes Schittny, Ruth Chiquet-Ehrismann

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)46-53
Number of pages8
JournalMatrix Biology
Volume40
DOIs
StatePublished - Nov 1 2014

Fingerprint

Stem Cell Niche
Tenascin
Vibrissae
Catenins
Knockout Mice
Mast Cells
Stem Cells
Adipocytes
Neural Crest
bcl-1 Genes
Melanocytes
Extracellular Matrix
Cell Membrane

Keywords

  • Beta-Catenin
  • Stem cell niche
  • Tenascin
  • Vibrissa
  • Whisker
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Tenascin-C is required for normal Wnt/β-catenin signaling in the whisker follicle stem cell niche. / Hendaoui, Ismaïl; Tucker, Richard P; Zingg, Dominik; Bichet, Sandrine; Schittny, Johannes; Chiquet-Ehrismann, Ruth.

In: Matrix Biology, Vol. 40, 01.11.2014, p. 46-53.

Research output: Contribution to journalArticle

Hendaoui, Ismaïl ; Tucker, Richard P ; Zingg, Dominik ; Bichet, Sandrine ; Schittny, Johannes ; Chiquet-Ehrismann, Ruth. / Tenascin-C is required for normal Wnt/β-catenin signaling in the whisker follicle stem cell niche. In: Matrix Biology. 2014 ; Vol. 40. pp. 46-53.
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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.",
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