Regulation of zebrafish melanocyte development by ligand-dependent BMP signaling.

Preventing terminal differentiation is important in the development and progression of many cancers including melanoma. Recent identification of the BMP ligand as a novel melanoma oncogene showed -activated BMP signaling suppresses differentiation of melanoma cells. Previous studies have identified roles for orthologs during early embryonic and neural crest development, but have not identified direct regulation of melanocyte development by GDF6. Here, we investigate the BMP ligand , a zebrafish ortholog of human , during the development of melanocytes from the neural crest. We establish that the loss of or inhibition of BMP signaling during neural crest development disrupts normal pigment cell development, leading to an increase in the number of melanocytes and a corresponding decrease in iridophores, another neural crest-derived pigment cell type in zebrafish. This shift occurs as pigment cells arise from the neural crest and depends on , an ortholog of , a key regulator of melanocyte development that is also targeted by oncogenic BMP signaling. Together, these results indicate that the oncogenic role ligand-dependent BMP signaling plays in suppressing differentiation in melanoma is a reiteration of its physiological roles during melanocyte development.