BMP-2 and BMP-4, but not BMP-6, increase the number of adrenergic cells which develop in quail trunk neural crest cultures.

The bone morphogenetic proteins (BMPs) are members of the TGF beta superfamily of growth factors. We have investigated the effects of BMP-2, BMP-4, and BMP-6 on the development of quail trunk neural crest cells in tissue culture. The presence of human recombinant BMP-2 or BMP-4 resulted in a dramatic increase in the number of tyrosine hydroxylase (TH)-immunoreactive cells which developed after 7 days in vitro. In contrast, BMP-6 showed little or no effect. Total cell number was not altered significantly by BMP-2, BMP-4, or BMP-6. However, in the presence of BMP-2 and BMP-4, but not BMP-6, the fraction of the cell population that became melanocytes was reduced to about two-thirds the control value. Addition of BMP-2 and BMP-4 also increased the number of Islet-1-immunoreactive and Hu-immunoreactive cells, but the magnitude of these increases was less than that observed for the TH-immunoreactive cell population. The Islet-1-immunoreactive cells were a subset of the TH-immunoreactive cells, while the Hu-positive cells were distinct from the TH-immunoreactive population. Analysis using bromodeoxyuridine labeling indicated that the increased numbers of TH-immunoreactive cells observed in the presence of BMP-2 and BMP-4 were not due to an increased rate of cell division in committed TH precursors. Further experiments, in which cultures were initiated from single cells, showed that the presence of BMP-2 resulted in colonies containing numerous catecholamine-positive cells without altering the overall number of colonies which survived and developed. In summary, our findings indicate that BMP-2 and BMP-4 are potent regulators of the adrenergic development of avian trunk neural crest cells.