P42 CHOREOGRAPHY OF MELANOCYTE MIGRATION INTO THE HAIR FOLLICLE AND SEGREGATION OF MELANOCYTE SUBPOPULATIONS DURING SKIN APPENDAGE MORPHOGENESIS

¹Peters E. M. J., ²Tobin D. J., ³Botchkareva N., ⁴Maurer M., ¹Paus R.; ¹Dept. of Dermatology, University Hospital Eppendorf, Hamburg, Germany; ²Dept. of Biomedical Sciences, University of Bradford, Bradford, UK; ³Dept. of Dermatology, Boston University School of Medicine, Boston, MA, USA; ⁴Dept. of Dermatology, University Hospital Johannes Gutenberg-University, Mainz, Germany

The stepwise generation of the hair follicle (HF) pigmentary unit offers an excellent model for studying develop-mental interactions between neural crest-derived and epithelial cells. Since melanocytes (MelC) express the stem cell factor (SCF) receptor, c-Kit, and depend on SCF for survival, migration and differentiation, we here examined c-Kit, SCF and S100 expression (a marker for melanogenic precursor cells) by immunoreactivity (IR) as well as MelC ultrastructure during HF morphogenesis in C57BL/6 mice. During stage 0-4 of HF development, prior to the onset of intrafollicular melanogenesis, strong c-Kit-IR was seen in selected non-melanized cells in the developing hair placode and hair plug. Many of these cells where also S 100-IR and were ultrastructually identified as melanoblasts. During the subsequent stages 5-8, c-Kit-IR cells achieved a more dendritic appearance and successively populated the developing outer root sheath and bulge region, to achieve their highest density in the hair bulb epithelium directly adjacent to the now fully developed dermal papilla. Interestingly, with the onset of pigment production in stage 4-5, c-Kit-IR cells in the proximal hair bulb increasingly concentrated below Auber´s line, while they disappeared from the outer root sheath and bulge by the finalization of HF morphogenesis (stage 8). By stage 8, electronmicroscopy demonstrated undifferentiated, non-pigmented MelC precursors in the outer rooth sheath, bulge, and below Auber´s line, alongside another population of fully differentiated MelC adjacent to the dermal papilla above Auber´s line. Widespread intraepithelial SCF-IR was seen during all stages of HF morphogenesis. This suggests that undifferentiated MelC and melanoblasts express c-Kit as as prerequisite for migration into the SCF-supplying HF epithelium, while adherence and differentiation that target these MelC subpopulations to defined territories in the hair follicle epithelium occure by as yet obscure mechanisms.