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 (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:

12 Mar 2021 04:36

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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