Twisted gastrulation can function as a BMP antagonist

Chenbei Chang, Douglas A. Holtzman, Samantha Chau, Troy Chickering, Elizabeth A. Woolf, Lisa M. Holmgren, Jana Bodorova, David P. Gearing, William E. Holmes and Ali H. Brivanlou ()
Additional contact information
Chenbei Chang: Laboratory of Vertebrate Molecular Embryology, The Rockefeller University, Box 32
Douglas A. Holtzman: Millennium Pharmaceuticals
Samantha Chau: Millennium Pharmaceuticals
Troy Chickering: Millennium Pharmaceuticals
Elizabeth A. Woolf: Millennium Pharmaceuticals
Lisa M. Holmgren: Millennium Pharmaceuticals
Jana Bodorova: Millennium Pharmaceuticals
David P. Gearing: Millennium Pharmaceuticals
William E. Holmes: Millennium Pharmaceuticals
Ali H. Brivanlou: Laboratory of Vertebrate Molecular Embryology, The Rockefeller University, Box 32

Nature, 2001, vol. 410, issue 6827, 483-487

Abstract: Abstract Bone morphogenetic proteins (BMPs), including the fly homologue Decapentaplegic (DPP), are important regulators of early vertebrate and invertebrate dorsal–ventral development1,2,3,4,5,6. An evolutionarily conserved BMP regulatory mechanism operates from fly to fish, frog and mouse to control the dorsal–ventral axis determination. Several secreted factors, including the BMP antagonist chordin/Short gastrulation (SOG)7,8,9,10,11,12, modulate the activity of BMPs. In Drosophila, Twisted gastrulation (TSG) is also involved in dorsal–ventral patterning13,14,15, yet the mechanism of its function is unclear. Here we report the characterization of the vertebrate Tsg homologues. We show that Tsg can block BMP function in Xenopus embryonic explants and inhibits several ventral markers in whole-frog embryos. Tsg binds directly to BMPs and forms a ternary complex with chordin and BMPs. Coexpression of Tsg with chordin leads to a more efficient inhibition of the BMP activity in ectodermal explants. Unlike other known BMP antagonists, however, Tsg also reduces several 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.

Date: 2001
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DOI: 10.1038/35068583

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