FIBROBLAST-DEPENDENT INDUCTION OF A MURINE SKIN LESION WITH SIMILARITY TO HUMAN COMMON BLUE NEVUS

In an attempt to define epithelial-mesenchymal interactions in skin ap pendage formation, we have been studying a nude mouse grafting model t hat permits the combination of heterotypic and heterochronic epithelia l and mesenchymal cells. In this study, using neonatal hair bud cells combined with various mesenchymal cell preparations, we show that one can regenerate near complete skin with intact epidermal and dermal lay ers plus mature hair follicles. It was determined that the character o f the resulting regenerated skin could be manipulated as a function of the specific mesenchymal component. Lack of dermal cells resulted in a scar, whereas inclusion of a suspension of dissociated total dermal cells resulted in near-complete skin regeneration, and in the presence of follicular papilla fibroblasts (both hair-inductive and non-hair-i nduct or NIH3T3 fibroblasts, the reconstitution had similarity, to the common blue nevus. The results indicate that 1) a simulant of human c ommon blue nevus can be produced in an animal model, 2) the underlying disorder of the lesion ire mice appears to be entirely dermal in orig in, arising independent of the epidermal component, and 3) complex der mal cell interactions involving lesion-initiative and lesion-suppressi ve activities underlie the pathogenesis. This experimental system will serve as a valuable tool in elucidating cutaneous dermal-epidermal si gnals in normal skin as well as the alteration of these signals in mal formations such as the hamartoma described here.