Abstract
Bone morphogenetic protein (BMP) signalling regulates embryonic dorsal–ventral cell fate decisions in flies, frogs and fish1. BMP activity is controlled by several secreted factors including the antagonists chordin and short gastrulation (SOG)2,3. Here we show that a second secreted protein, Twisted gastrulation (Tsg)4, enhances the antagonistic activity of Sog/chordin. In Drosophila, visualization of BMP signalling using anti-phospho-Smad staining5 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 Tsg function in zebrafish with morpholino oligonucleotides causes ventralization similar to that produced by chordin mutants. Co-injection of sub-inhibitory levels of morpholines directed against both Tsg and chordin synergistically enhances the penetrance of the ventralized phenotype. We show that Tsgs from different species are functionally equivalent, and conclude that Tsg is a conserved protein that functions with SOG/chordin to antagonize BMP signalling.
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Acknowledgements
We are grateful to K. Cho, D. Greenspan and A. Hemmati-Brivanlou for communication of results before publication and to E. De Robertis for comments on the manuscript. We thank M. Tsang at R&D systems for a gift of purified mouse chordin; D. Greenspan for purified mouse Tsg-C protein; J. Groppe for purified Dpp; P. ten Dijke for the gift of anti-phospho Mad; and E. De Robertis for the Xenopus Tsg cDNA clone. We also thank E. Hirsch for assistance with the mouse FISH analysis. This work was supported by NIH grants to J.L.M, M.B.O and S.C.E. O.S. was supported by Nippon Roche K.K. A.P. was supported by a training grant from the NIH. M.B.O. is an Associate Investigator for the Howard Hughes Medical Institute.
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Ross, J., Shimmi, O., Vilmos, P. et al. Twisted gastrulation is a conserved extracellular BMP antagonist. Nature 410, 479–483 (2001). https://doi.org/10.1038/35068578
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DOI: https://doi.org/10.1038/35068578
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