Twisted gastrulation can function as a BMP antagonist

Bone morphogenetic proteins (BMPs), including the fly homologue Decapentapl egic (DPP), are important regulators of early vertebrate and invertebrate d orsal-ventral development(1-6). An evolutionarily conserved BMP regulatory mechanism operates from fly to fish, frog and mouse to control the dorsal-v entral axis determination. Several secreted factors, including the BMP anta gonist chordin/Short gastrulation (SOG)(7-12), modulate the activity of BMP s. In Drosophila, Twisted gastrulation (TSG) is also involved in dorsal-ven tral patterning(13-15), yet the mechanism of its function is unclear. Here we report the characterization of the vertebrate Tsg homologues. We show th at Tsg can block BMP function in Xenopus embryonic explants and inhibits se veral ventral markers in whole-frog embryos. Tsg binds directly to BMPs and forms a ternary complex with chordin and BMPs. Coexpression of Tsg with ch ordin leads to a more efficient inhibition of the BMP activity in ectoderma l explants. Unlike other known BMP antagonists, however, Tsg also reduces s everal anterior markers at late developmental stages. Our data suggest that Tsg can function as a BMP inhibitor in Xenopus; furthermore, Tsg may have additional functions during frog embryogenesis.