SPECIFICITY OF BONE MORPHOGENETIC PROTEIN-RELATED FACTORS - CELL FATEAND GENE-EXPRESSION CHANGES IN DROSOPHILA EMBRYOS INDUCED BY DECAPENTAPLEGIC BUT NOT 60A

Reported assays of the bone morphogenetic proteins (BMPs) have not in general revealed specific functions for the different proteins, belyin g the specificity implied by the evolutionary conservation and distinc t expression patterns of the genes encoding BMPs. We have used assays of developmental function to show that the two Drosophila homologues o f the BMPs, decapentaplegic (dpp) and 60A, that both induce ectopic bo ne formation in mammalian assay systems, have distinct effects in Dros ophila development. A binary expression system using the yeast transcr iptional activator GAL4 directed identical patterns of tissue and temp orally specific dpp and 60A expression. When dpp enhancer elements dro ve GAL4 expression, GAL4-responsive dpp transgenes rescued dpp mutant phenotypes, but GAL4-responsive 60A transgenes did not. Ectopic ectode rmal expression of dpp during gastrulation respecified the dorsal/vent ral pattern of the embryo. In contrast, ectopic 60A expression had no detectable effects on embryonic development but led to defects in adul t structures or lethality during metamorphosis. Expression of 60A in c ells expressing dpp did not interfere with dpp functions, indicating t hat dysfunctional heterodimers did not form at sufficient levels to in hibit dpp. These specific developmental responses in Drosophila indica te that in vivo functions of BMP-like factors can be more specific tha n indicated by the ectopic bone formation assays and that the Drosophi la embryo provides an assay system sensitive to the structural differe nces that contribute to BMP specificity in vivo.