Twisted gastrulation is a conserved extracellular BMP antagonist.
Bone morphogenetic protein (BMP) signalling regulates embryonic dorsal-ventral cell fate decisions in flies, frogs and fish. BMP activity is controlled by several secreted factors including the antagonists chordin and short gastrulation (SOG). Here we show that a second secreted protein, Twisted gastrulation (Tsg), enhances the antagonistic activity of Sog/chordin. In Drosophila, visualization of BMP signalling using anti-phospho-Smad staining 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.
Department of Genetics, Howard Hughes Medical Institute, University of Minnesota, Minneapolis 55455, USA.
J J
JJ
Ross
O
O
Shimmi
P
P
Vilmos
A
A
Petryk
H
H
Kim
K
K
Gaudenz
S
S
Hermanson
S C
SC
Ekker
M B
MB
O'Connor
J L
JL
Marsh
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004330:Drosophila; D029721:Drosophila Proteins; D005775:Gastrula / Q000378:metabolism*; D015870:Gene Expression; D006023:Glycoproteins; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014981:Xenopus; D015027:Zebrafish
D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; D019476:Insect Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C090223:TSG protein, Drosophila; C091428:sog protein, Drosophila; C054234:chordin