ENDOTHELIN-3 PROMOTES NEURAL CREST CELL-PROLIFERATION AND MEDIATES A VAST INCREASE IN MELANOCYTE NUMBER IN CULTURE

Mutations in the endothelin 3 (EDN3) gene severely affect the developm ent of neural crest-derived melanocytes. In this paper, we report the action of EDN3 on neural crest cells in vitro. The presence of EDN3 le ads to a large increase in the number of cells, the majority of which eventually differentiate into melanocytes that aggregate to form a rep roducible pigmentation pattern. Quantitative analysis of the effect of different culture conditions revealed that EDN3 initially promotes ne ural crest cell proliferation. This phase of expansion, which can be p rolonged for a few weeks if the cells are replated regularly, is follo wed by both a decrease in cell proliferation and the onset of melanocy tic differentiation. Therefore, EDN3 is a potent mitogen for early neu ral crest cell precursors that can give rise to melanocytes.