Regional Control of Hairless versus Hair-Bearing Skin by Dkk2
Yaolin Song,
Ana C. Boncompagni,
Sang-Seok Kim,
Heather R. Gochnauer,
Yuhang Zhang,
Gabriela G. Loots,
Dianqing Wu,
Yulin Li,
Mingang Xu,
Sarah E. Millar
Affiliations
Yaolin Song
The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, PRC; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Ana C. Boncompagni
Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Sang-Seok Kim
Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Dermatology, Hallym University Kangdong Sacred Heart Hospital, Seoul 134-701, Korea
Heather R. Gochnauer
Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Yuhang Zhang
The James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA
Gabriela G. Loots
School of Natural Sciences, University of California, Merced, CA 95343, USA; Biology and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
Dianqing Wu
Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA
Yulin Li
The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, PRC
Mingang Xu
Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Corresponding author
Sarah E. Millar
Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA; Corresponding author
Summary: 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 gradually becomes patterned, mimicking follicular development in normally haired areas. These data provide a paradigm in which regionally restricted expression of a Wnt inhibitor underlies specification of hairless versus hairy skin. : What controls formation of hairless versus hairy skin? Song et al. find the secreted Wnt inhibitor Dkk2 is specifically expressed in embryonic mouse hairless, but not in rabbit hair-bearing, plantar skin. Mouse Dkk2 deletion permits plantar hair formation. Thus, evolutionary changes in Dkk2 expression contribute to species-specific hair patterns. Keywords: Dickkopf 2, Wnt, secreted Wnt inhibitor, skin development, hair follicle, plantar skin, hairless skin, mouse mutant, skin patterning, rabbit embryo
