BMP-2 stimulates tyrosinase gene expression and melanogenesis in differentiated melanocytes

Cells of the vertebrate neural crest (crest cells) differentiate in vitro t o melanocytes and sympathoadrenal (SA) progenitor cells. We have shown prev iously, using primary J. quail neural crest cultures, the combinatorial eff ect of bone morphogenetic protein-2 (BMP-2) and cAMP signaling on SA cell d evelopment. Herein, we report that in primary J. quaff neural crest culture s, BMP-2 and cAMP signaling similarly exert a combinatorial effect on melan ocyte development. We demonstrate that BMP-2 treatment of neural crest cell s increases melanogenesis by promoting the synthesis of melanin. This incre ased melanin synthesis by BMP-2 is effected by the selective increase in th e transcription of the tyrosinase gene, encoding the rate-limiting enzyme o f the melanin biosynthetic pathway. By contrast, BMP-2 exerts no effect on the expression of the tyrosine-related proteins 1 and 2 (TyrpI and Dct), al so involved in the melanin biosynthetic process, or on the expression of mi crophalmia (Mitf) gene, supporting the fact that BMP-2 does not affect mela nocyte differentiation. Employing transient transfection analysis of tyrosi nase-reporter constructs in B16 melanoma cells, we demonstrate that the BMP -2 response-element is localized between 900 and 1,100 bp upstream from the tyrosinase transcriptional start site. These studies support a role for BM P-2 in melanogenesis by selectively targeting the expression of the tyrosin ase gene involved in melanin biosynthesis.