title: CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth.
abstract: Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment.
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Linli
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Division of Pediatric Ophthalmology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: April
authors.initials: A
authors.lastname: Carpenter
authors.affiliation: Division of Pediatric Ophthalmology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
authors.affiliation: Burnett School of Biological Sciences, University of Central Florida, Orlando, FL 32816, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Andl
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000818:Animals; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D008024:Ligands; C000606023:PROM1 protein, human; D051153:Wnt Proteins
keywords: Wnt proteins; Wnt signaling; Wntless; dermal papilla; hair cycle; hair follicle