Epithelial Wnt ligand secretion is required for adult hair follicle growth and regeneration.
β-Catenin, a key transducer molecule of Wnt signaling, is required for adult hair follicle growth and regeneration. However, the cellular source of Wnt ligands required for Wnt/β-catenin activation during anagen induction is unknown. In this study, we genetically deleted Wntless (Wls), a gene required for Wnt ligand secretion by Wnt-producing cells, specifically in the hair follicle epithelium during telogen phase. We show that epithelial Wnt ligands are required for anagen, as loss of Wls in the follicular epithelium resulted in a profound hair cycle arrest. Both the follicular epithelium and dermal papilla showed markedly decreased Wnt/β-catenin signaling during anagen induction compared with control hair follicles. Surprisingly, hair follicle stem cells that are responsible for hair regeneration maintained expression of stem cell markers but exhibited significantly reduced proliferation. Finally, we demonstrate that epidermal Wnt ligands are critical for adult wound-induced de novo hair formation. Collectively, these data show that Wnt ligands secreted by the hair follicle epithelium are required for adult hair follicle regeneration and provide new insight into potential cellular targets for the treatment of hair disorders such as alopecia.
Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA.
Peggy S
PS
Myung
Makoto
M
Takeo
Mayumi
M
Ito
Radhika P
RP
Atit
D000818:Animals; D049109:Cell Proliferation; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D017353:Gene Deletion; D018859:Hair Follicle / Q000254:growth & development*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008024:Ligands; D051379:Mice; D043562:Receptors, G-Protein-Coupled; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000254:growth & development / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism / Q000502:physiology
C545200:Gpr177 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D051176:beta Catenin