R. Lahav et al., ENDOTHELIN-3 PROMOTES NEURAL CREST CELL-PROLIFERATION AND MEDIATES A VAST INCREASE IN MELANOCYTE NUMBER IN CULTURE, Proceedings of the National Academy of Sciences of the United Statesof America, 93(9), 1996, pp. 3892-3897
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.