biostudies-literatureSong YPenn Skin Diseases Research CenterNational Institutes of Health (NIH), USADermatology FoundationNCI NIH HHSNIAMS NIH HHSChina Scholarship Council, ChinaNIGMS NIH HHSPenn Skin Biology and Diseases Resource-based Center2981-2991.e3https://www.ebi.ac.uk/biostudies/studies/S-EPMC6345517biostudies-literatureUnknown25(11)Haired skin is a defining characteristic of mammals. However, some specialized skin regions, such as human palms, soles and ventral wrist, and mouse plantar foot, are entirely hairless. Using mouse plantar skin as a model system, we show that the endogenous secreted Wnt inhibitor DKK2 suppresses plantar hair follicle development and permits the formation of hairless skin. Plantar skin retains all of the mechanistic components needed for hair follicle development, as genetic deletion of Dkk2 permits formation of fully functional plantar hair follicles that give rise to external hair, contain sebaceous glands and a stem cell compartment, and undergo regenerative growth. In the absence of Dkk2, Wnt/β-catenin signaling activity is initially broadly elevated in embryonic plantar skin and graduaCell reportsRegional Control of Hairless versus Hair-Bearing Skin by Dkk2.PMC6345517P30AR057217R01 GM112182P30 AR057217P30AR069589R01 AR047709R37AR047709R01 CA214703P30 AR069589R01 CA139395R37 AR047709Boncompagni ACGochnauer HRLi YXu MKim SSZhang YLoots GGWu DMillar SESong YfalseRegional Control of Hairless versus Hair-Bearing Skin by Dkk2.Haired skin is a defining characteristic of mammals. However, some specialized skin regions, such as human palms, soles and ventral wrist, and mouse plantar foot, are entirely hairless. Using mouse plantar skin as a model system, we show that the endogenous secreted Wnt inhibitor DKK2 suppresses plantar hair follicle development and permits the formation of hairless skin. Plantar skin retains all of the mechanistic components needed for hair follicle development, as genetic deletion of Dkk2 permits formation of fully functional plantar hair follicles that give rise to external hair, contain sebaceous glands and a stem cell compartment, and undergo regenerative growth. In the absence of Dkk2, Wnt/β-catenin signaling activity is initially broadly elevated in embryonic plantar skin and gradua2018-01-01T00:00:00Z2018 Dec2026-04-15T15:10:10.973Z2019-03-26T22:41:06ZS-EPMC63455173050955710.1016/j.celrep.2018.11.017