SCF/c-kit signaling is required for cyclic regeneration of the hair pigmentation unit

Hair graying, an age-associated process of unknown etiology, is characteriz ed by a reduced number and activity of hair follicle (HF) melanocytes, Stem cell factor (SCF) and its receptor c-kit are important for melanocyte surv ival during development, and mutations in these genes result in unpigmented hairs. Here we show that during cyclic HF regeneration in C57BL/6 mice, pr oliferating, differentiating, and melanin-producing melanocytes express c-k it, whereas presumptive melanocyte precursors do not, SCF overexpression in HF epithelium significantly increases the number and proliferative activit y of melanocytes, During the induced hair cycle in C57BL/6 mice, administra tion of anti-c-kit antibody dose-dependently decreases hair pigmentation an d leads to partially depigmented (gray) or fully depigmented (white) hairs, associated with significant decreases in melanocyte proliferation and diff erentiation, as determined by immunostaining and confocal microscopy, Howev er, in the next hair cycle, the previously treated animals grow fully pigme nted hairs with the normal number and distribution of melanocytes, This sug gests that melanocyte stem cells are not dependent on SCF/c-kit and when ap propriately stimulated can generate melano-genically active melanocytes, Th erefore, the blockade of c-kit signaling offers a fully reversible model fo r hair depigmentation, which might be used for the studies of hair pigmenta tion disorders.-Botchkareva, N. V., Khlgatian, M., Longley, B. J., Botchkar ev, V. A., and Gilchrest, B. A. SCF/c-kit signaling is required for cyclic regeneration of the hair pigmentation unit.