Migration of Melanoblasts into the Developing Murine Hair Follicle Is Accompanied by Transient c-Kit ExpressionEva M. J. Petersa,b, Desmond J. Tobinc, Natasha Botchkarevaa, Marcus Maurerd, and Ralf Pausaa Department of Dermatology, University Hospital Eppendorf, University of Hamburg, Germany b Chamlé, Campus Virchow Clinic, Berlin, Germany c Department of Biomedical Sciences, University of Bradford, Bradford, United Kingdom d Department of Dermatology, University Hospital Johannes GutenbergUniversity, Mainz, Germany Correspondence to: Ralf Paus, Dept. of Dermatology, University Hospital Eppendorf, University of Hamburg, Martinistr. 52, D-20246 Hamburg, Germany. E-mail: paus@uke.uni-hamburg.de Disruption of the c-Kit/stem cell factor (SCF) signaling pathway interferes with the survival, migration, and differentiation of melanocytes during generation of the hair follicle pigmentary unit. We examined c-Kit, SCF, and S100 (a marker for precursor melanocytic cells) expression, as well as melanoblast/melanocyte ultrastructure, in perinatal C57BL/6 mouse skin. Before the onset of hair bulb melanogenesis (i.e., stages 04 of hair follicle morphogenesis), strong c-Kit immunoreactivity (IR) was seen in selected non-melanogenic cells in the developing hair placode and hair plug. Many of these cells were S100-IR and were ultrastructurally identified as melanoblasts with migratory appearance. During the subsequent stages (5 and 6), increasingly dendritic c-Kit-IR cells successively invaded the hair bulb, while S100-IR gradually disappeared from these cells. Towards the completion of hair follicle morphogenesis (stages 7 and 8), several distinct follicular melanocytic cell populations could be defined and consisted broadly of (a) undifferentiated, non-pigmented c-Kit-negative melanoblasts in the outer root sheath and bulge and (b) highly differentiated melanocytes adjacent to the hair follicle dermal papilla above Auber's line. Widespread epithelial SCF-IR was seen throughout hair follicle morphogenesis. These findings suggest that melanoblasts express c-Kit as a prerequisite for migration into the SCF-supplying hair follicle epithelium. In addition, differentiated c-Kit-IR melanocytes target the bulb, while non-c-Kit-IR melanoblasts invade the outer root sheath and bulge in fully developed hair follicles. (J Histochem Cytochem 50:751766, 2002) Key Words: hair follicle morphogenesis, c-Kit, stem cell factor, S100, C57BL/6 mouse, melanoblast, melanocyte, immunohistochemistry, ultrastructure
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