The appropriateness of this system was validated by faithful depletion of KROX20 cells in vivo after doxycycline induction (Fig. is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes. is deleted in lineage cells. We also demonstrate that deletion of lineage cells in vivo results in a complete arrest of new hair growth, demonstrating the crucial role of lineage cells in hair development. Results Mice lacking SCF in lineage cells exhibit progressive hair graying While studying the role of mast cells and SCF during the initiation of neurofibroma, a Schwann cell neoplasm, we conditionally deleted in neurofibroma neoplastic cells using the Schwann cell lineage mouse collection. Serendipitously, we found that the mice without SCF in lineage cells developed hair graying and, early in life, lost Candesartan cilexetil (Atacand) all hair pigmentation. Rabbit polyclonal to HIP Invariably, all mice (= 20) displayed progressive hair graying. The first round of hair graying occurred homogenously during postnatal days 30C40 (P30CP40). As the mice aged, the hairs underwent further depigmentation in waves. This switch converted all black pigmented hairs to white within 9 mo (Fig. 1A; Supplemental Fig. S1A). We believe that this pattern of hair color change is usually associated with the mouse hair cycle when aged hairs are replaced by newly generated hairs (Plikus and Chuong 2008; Shimomura and Christiano 2010). Open in a separate window Physique 1. Mice lacking SCF in lineage cells exhibit Candesartan cilexetil (Atacand) progressive hair graying. (mouse (control (= 20. (mice showed distinct pigment levels in distal and proximal ends; newly developed hairs in the proximal side Candesartan cilexetil (Atacand) (arrowheads) were absent of pigment. (mice. (mice at P9 followed by a rapid loss of pigmentation beginning from the hair matrix (arrowheads) at P11 and P13. (mice at P11 and P13. (showing a significant reduction of melanin density in graying hair shafts. Melanin density was analyzed by ImageJ. Data are mean SEM from 100 randomly selected HFs in each group. (****) 0.0001. (mice were depilated to stimulate hair regeneration; new hair shafts were completely absent of pigment. = 3. Nuclei were stained with nuclear Fast Red in mice, we first analyzed the pelage hair shafts plucked from P20 dorsal skin. Interestingly, the amount of pigment at the distal and proximal ends of each hair shaft was quite different; the amount of pigment at the distal appeared normal, but the pigment was mostly absent from your proximal end (Fig. 1B). Fontana-Masson staining confirmed that this hypopigmentation was caused by the absence of melanin in the hair shaft cortex and medulla (the compartments housing the most melanin in pigmented hair shaft) (Fig. 1C). We then decided the time of onset of decreased pigmentation. The amount of pigment in individual hairs appeared normal at P9 (Fig. 1D), with the loss of hair pigmentation becoming apparent at P11; it progressed quickly after that (Fig. 1D,E). Analysis of melanin density in the HF revealed significant reductions at P11 and P13 ( 0.0001) (Fig. 1F), explaining the early loss of hair pigmentation in mice (Fig. 1B). mice exhibited progressive hair graying; their coat color underwent a dynamic change from black to white within 9 mo (Fig. 1A; Supplemental Fig. S1A). However, their newly synthesized hairs were already largely depigmented at P20 (Fig. 1B). These results suggested that this long period of hair graying is Candesartan cilexetil (Atacand) due to the mixture of partly pigmented (aged) and unpigmented (new) hair shafts (Supplemental Fig. S1B,C) rather than the continuous production of new gray hairs. To confirm this, gray mice were depilated at 2 mo to remove all hairs, including aged hairs, and stimulate new hair regeneration; as expected, their new hairs showed a complete loss of pigmentation (Fig. 1G). Most importantly, Candesartan cilexetil (Atacand) the fact that mice underwent a complete.