title: Distinct functions for Wnt/β-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis.
abstract: 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.
authors: Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors: Yeon Sook
authors: YS
authors: Choi
authors: Yuhang
authors: Y
authors: Zhang
authors: Mingang
authors: M
authors: Xu
authors: Yongguang
authors: Y
authors: Yang
authors: Mayumi
authors: M
authors: Ito
authors: Tien
authors: T
authors: Peng
authors: Zheng
authors: Z
authors: Cui
authors: Andras
authors: A
authors: Nagy
authors: Anna-Katerina
authors: AK
authors: Hadjantonakis
authors: Richard A
authors: RA
authors: Lang
authors: George
authors: G
authors: Cotsarelis
authors: Thomas
authors: T
authors: Andl
authors: Edward E
authors: EE
authors: Morrisey
authors: Sarah E
authors: SE
authors: Millar
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D017353:Gene Deletion; D018859:Hair Follicle / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D006706:Homeostasis; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D009154:Mutation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D051176:beta Catenin