Distinct Functions for Wnt/β-Catenin in Hair Follicle Stem Cell Proliferation and Survival and Interfollicular Epidermal Homeostasis

• Published in: Cell stem cell 2013-12, Vol.13 (6), p.720-733
• Main Authors: Choi, Yeon Sook, Zhang, Yuhang, Xu, Mingang, Yang, Yongguang, Ito, Mayumi, Peng, Tien, Cui, Zheng, Nagy, Andras, Hadjantonakis, Anna-Katerina, Lang, Richard A., Cotsarelis, George, Andl, Thomas, Morrisey, Edward E., Millar, Sarah E.
• Format: Article
• Language: English
• Subjects: Animals; beta Catenin - metabolism; Biomarkers - metabolism; Cell Proliferation; Cell Survival; Gene Deletion; Hair Follicle - cytology; Hair Follicle - embryology; Hair Follicle - metabolism; Homeostasis; Intercellular Signaling Peptides and Proteins - metabolism; Mice; Mutation; Stem Cells - cytology; Stem Cells - metabolism; Wnt Proteins - metabolism; Wnt Signaling Pathway
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2013.10.003

Wnt/β-catenin signaling is a central regulator of adult stem cells. Variable sensitivity of Wnt reporter transgenes, β-catenin’s dual roles in adhesion and signaling, and hair follicle degradation and inflammation resulting from broad deletion of epithelial β-catenin have precluded clear understanding of Wnt/β-catenin’s functions in adult skin stem cells. By inducibly deleting β-catenin globally in skin epithelia, only in hair follicle stem cells, or only in interfollicular epidermis and comparing the phenotypes with those caused by ectopic expression of the Wnt/β-catenin inhibitor Dkk1, we show that this pathway is necessary for hair follicle stem cell proliferation. However, β-catenin is not required within hair follicle stem cells for their maintenance, and follicles resume proliferating after ectopic Dkk1 has been removed, indicating persistence of functional progenitors. We further unexpectedly discovered a broader role for Wnt/β-catenin signaling in contributing to progenitor cell proliferation in nonhairy epithelia and interfollicular epidermis under homeostatic, but not inflammatory, conditions. [Display omitted] •Epithelial Wnt/β-catenin signaling is required for hair matrix cell proliferation•LRP inhibition permits stem cell survival and blocks hair growth reversibly•β-catenin is required in bulge stem cells for their proliferation, but not survival•β-catenin signaling contributes to proliferation of interfollicular epidermis β-catenin signaling is required within hair follicle stem cells for their proliferation, but not their survival, and plays an unexpected pro-proliferative role in normal interfollicular epidermis and nonhairy epithelia.