Ross J J, Shimmi O, Vilmos P, Petryk A, Kim H, Gaudenz K, Hermanson S, Ekker S C, O'Connor M B, Marsh J L
Department of Genetics, Howard Hughes Medical Institute, University of Minnesota, Minneapolis 55455, USA.
Nature. 2001 Mar 22;410(6827):479-83. doi: 10.1038/35068578.
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.
骨形态发生蛋白（BMP）信号通路调控果蝇、青蛙和鱼类胚胎的背腹细胞命运决定。BMP活性受多种分泌因子控制，包括拮抗剂脊索蛋白和短原肠作用蛋白（SOG）。在此我们表明，另一种分泌蛋白扭曲原肠作用蛋白（Tsg）可增强Sog/脊索蛋白的拮抗活性。在果蝇中，使用抗磷酸化Smad染色观察BMP信号通路，结果显示tsg和sog功能丧失表型非常相似。在S2细胞和成虫盘（imaginal discs）中，TSG和SOG共同作用时比单独作用时更能有效抑制BMP信号通路。用吗啉代寡核苷酸阻断斑马鱼中的Tsg功能会导致腹化，类似于脊索蛋白突变体产生的表型。共同注射针对Tsg和脊索蛋白的亚抑制水平吗啉代寡核苷酸可协同增强腹化表型的外显率。我们表明不同物种的Tsg在功能上是等效的，并得出结论：Tsg是一种保守蛋白，与SOG/脊索蛋白共同作用以拮抗BMP信号通路。
