| First Author | Hendaoui I | Year | 2014 |
| Journal | Matrix Biol | Volume | 40 |
| Pages | 46-53 | PubMed ID | 25196097 |
| Mgi Jnum | J:220409 | Mgi Id | MGI:5634626 |
| Doi | 10.1016/j.matbio.2014.08.017 | Citation | Hendaoui I, et al. (2014) Tenascin-C is required for normal Wnt/beta-catenin signaling in the whisker follicle stem cell niche. Matrix Biol 40:46-53 |
| abstractText | 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/beta-catenin signaling promotes melanogenesis and suppresses the differentiation of adipocytes and mast cells, we analyzed beta-catenin subcellular localization in the trabecular niche. We found cytoplasmic and nuclear beta-catenin in wild-type mice reflecting active Wnt/beta-catenin signaling, whereas beta-catenin in tenascin-C knockout mice was mostly cell membrane-associated and thus transcriptionally inactive. Furthermore, cells expressing the Wnt/beta-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 beta-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/beta-catenin signaling in the niche thereby maintaining the stem cell pool and suppressing aberrant differentiation, while in the knockout mice with reduced Wnt/beta-catenin signaling, stem cells from the trabecular niche can differentiate into ectopic adipocytes and mast cells. |
