Scott I C, Blitz I L, Pappano W N, Maas S A, Cho K W, Greenspan D S
Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison 53706, USA.
Nature. 2001 Mar 22;410(6827):475-8. doi: 10.1038/35068572.
Twisted gastrulation (TSG) is involved in specifying the dorsal-most cell fate in Drosophila embryos, but its mechanism of action is poorly understood. TSG has been proposed to modify the action of Short gastrulation (SOG), thereby increasing signalling by the bone morphogenetic protein (BMP) Decapentaplegic. SOG, an inhibitor of BMP signalling, is in turn inactivated by the protease Tolloid. Here we identify Tsg gene products from human, mouse, Xenopus, zebrafish and chick. Expression patterns in mouse and Xenopus embryos are consistent with in vivo interactions between Tsg, BMPs and the vertebrate SOG orthologue, chordin. We show that Tsg binds both the vertebrate Decapentaplegic orthologue BMP4 and chordin, and that these interactions have multiple effects. Tsg increases chordin's binding of BMP4, potentiates chordin's ability to induce secondary axes in Xenopus embryos, and enhances chordin cleavage by vertebrate tolloid-related proteases at a site poorly used in Tsg's absence; also, the presence of Tsg enhances the secondary axis-inducing activity of two products of chordin cleavage. We conclude that Tsg acts as a cofactor in chordin's antagonism of BMP signalling.
扭曲原肠胚形成（TSG）参与果蝇胚胎中最背侧细胞命运的特化，但其作用机制尚不清楚。有人提出TSG可改变短原肠胚形成（SOG）的作用，从而增强骨形态发生蛋白（BMP）脱尾蛋白的信号传导。SOG是BMP信号传导的抑制剂，反过来又被蛋白酶Tolloid灭活。在这里，我们鉴定了来自人类、小鼠、非洲爪蟾、斑马鱼和鸡的Tsg基因产物。小鼠和非洲爪蟾胚胎中的表达模式与Tsg、BMP和脊椎动物SOG直系同源物脊索蛋白之间的体内相互作用一致。我们表明，Tsg与脊椎动物脱尾蛋白直系同源物BMP4和脊索蛋白都结合，并且这些相互作用具有多种效应。Tsg增加脊索蛋白对BMP4的结合，增强脊索蛋白在非洲爪蟾胚胎中诱导次生轴的能力，并增强脊椎动物类Tolloid蛋白酶在缺乏Tsg时很少使用的位点对脊索蛋白的切割；此外，Tsg的存在增强了脊索蛋白切割的两种产物的次生轴诱导活性。我们得出结论，Tsg在脊索蛋白对BMP信号传导的拮抗作用中起辅助因子的作用。
