077 Further evidence for an involvement of hepatocyte growth factor /scatter factor (HGF/SF) and Met signaling in hair growth control and in follicular pigmentation

Gerd Lindner1, Glenn Merlino2, Sven Mueller-Roever1 and Ralf Paus1 1Dept of Dermatology, University of Hamburg, Germany, 2Laboratory of Molecular Biology, National Cancer Institute, USA

HGF/SF and its cognate receptor Met are principal mediators of mesenchymal-epithelial interactions. HGF/SF overexpressing transgenic mice, under the control of the MT-1 promoter, display accelerated HF morphogenesis and show retarded catagen development (FASEB J 2000;14:319) suggesting an important role of this factor in the control of hair follicle (HF) growth. Therefore, HF morphology and immunoreactive (IR) expression patterns of HGF/SF and Met, as well as that of TRP-1 (a key melanogenesis-associated protein) were studied in HGF/SF-transgenic mice during HF morphogenesis and cycling. Similar to pharmacologically-induced hair growth by cyclosporin A (JID 1998; 110;632a), HGFtransgenic mice displayed premature HGF/SF IR in the dermal papilla of very early anagen HFs, suggesting a potential mechanism of accelerated anagen development in these mice. Interestingly, the stringently localized appearance of HGF/SF expression within dermal papilla fibroblasts of WT mice was abrogated in the regressing epithelial strand and germ capsule of transgenic catagen VII HF. Here, HGF/SF IR was coexpressed with Met IR in keratinocytes, i.e. within the epithelium. At the epidermal/dermal border, ectopic melanocytes were detected, which highly expressed HGF/SF IR. Sporadically, adult transgenic mice developed a severe skin phenotyp with highly abnormal HF morphology. In these sections, follicles showed a grossly enlarged epithelial strand and displayed two dermal papillae in one single HF. This further support that HGF/SF and Met operate as powerful hair follicle morphogens and suggest that this signaling system is involved in the control of intrafollicular pigmentation.