Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding.
The mammalian hair follicle is a complex 'mini-organ' thought to form only during development; loss of an adult follicle is considered permanent. However, the possibility that hair follicles develop de novo following wounding was raised in studies on rabbits, mice and even humans fifty years ago. Subsequently, these observations were generally discounted because definitive evidence for follicular neogenesis was not presented. Here we show that, after wounding, hair follicles form de novo in genetically normal adult mice. The regenerated hair follicles establish a stem cell population, express known molecular markers of follicle differentiation, produce a hair shaft and progress through all stages of the hair follicle cycle. Lineage analysis demonstrated that the nascent follicles arise from epithelial cells outside of the hair follicle stem cell niche, suggesting that epidermal cells in the wound assume a hair follicle stem cell phenotype. Inhibition of Wnt signalling after re-epithelialization completely abrogates this wounding-induced folliculogenesis, whereas overexpression of Wnt ligand in the epidermis increases the number of regenerated hair follicles. These remarkable regenerative capabilities of the adult support the notion that wounding induces an embryonic phenotype in skin, and that this provides a window for manipulation of hair follicle neogenesis by Wnt proteins. These findings suggest treatments for wounds, hair loss and other degenerative skin disorders.
Ito
Mayumi
M
Department of Dermatology, Kligman Laboratories, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Yang
Zaixin
Z
Andl
Thomas
T
Cui
Chunhua
C
Kim
Noori
N
Millar
Sarah E
SE
Cotsarelis
George
G
D000818:Animals; D019070:Cell Lineage; D004847:Epithelial Cells / Q000166:cytology; D018859:Hair Follicle / Q000166:cytology* / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology; D051153:Wnt Proteins / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology
D051153:Wnt Proteins