Twisted gastrulation is a conserved extracellular BMP antagonist

Bone morphogenetic protein (BMP) signalling regulates embryonic dorsal-vent ral cell fate decisions in flies, frogs and fish(1). BMP activity is contro lled by several secreted factors including the antagonists chordin and shor t gastrulation (SOG)(2,3). Here we show that a second secreted protein, Twi sted gastrulation (Tsg)(4), enhances the antagonistic activity of Sog/chord in. In Drosophila, visualization of BMP signalling using anti-phospho-Smad staining(5) shows that the tsg and sog loss-of-function phenotypes are very similar. In S2 cells and imaginal discs, TSG and SOG together make a more effective inhibitor of BMP signalling than either of them alone. Blocking T sg function in zebrafish with morpholino oligonucleotides causes ventraliza tion similar to that produced by chordin mutants. Co-injection of sub-inhib itory levels of morpholines directed against both Tsg and chordin synergist ically enhances the penetrance of the ventralized phenotype. We show that T sgs from different species are functionally equivalent, and conclude that T sg is a conserved protein that functions with SOG/chordin to antagonize BMP signalling.