Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizer
Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizer
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DOI：
10.1038/35001602
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发表时间：
2000-02-17
期刊：
影响因子：
64.8
通讯作者：
Cho, KWY
中科院分区：
文献类型：
--
作者：
Nishita, M;Hashimoto, MK;Cho, KWY
Wnt和TGF-β超家族的成员在发育和组织维持过程中调节细胞命运和增殖（1-3）。在早期两栖动物胚胎中，Wnt和TGF-β超家族信号级联是建立背侧信号中心（Spemann's organizer）所必需的（4-8）。两种途径的细胞内蛋白质在活化后移位到细胞核参与转录。在这里，我们表明，β-连环蛋白和Lef 1/Tcf，这是下游组件的Wnt信号级联，形成一个复杂的Smad 4，一个必不可少的调解员的信号启动的TGF-β生长因子超家族的成员。在非洲爪蟾，这种相互作用直接和协同影响双（Xtwn）基因的表达在形成的组织者。据我们所知，这是体内TGF-β和Wnt信号传导组分之间物理相互作用的第一个证明。
Members of the Wnt and TGF-beta superfamilies regulate both cell fate and proliferation during development and tissue maintenance(1-3). In the early amphibian embryo, the Wnt and TGF-beta superfamily signalling cascades are required for the establishment of a dorsal signalling centre, Spemann's organizer(4-8). Intracellular proteins of both pathways, upon activation, translocate to the nucleus to participate in transcription. Here we show that beta-catenin and Lef1/Tcf, which are downstream components of the Wnt signalling cascade, form a complex with Smad4, an essential mediator of signals initiated by members of the TGF-beta growth factor superfamily. In Xenopus, this interaction directly and synergistically affects expression of the twin (Xtwn) gene during formation of the organizer. This is, to our knowledge, the first demonstration of a physical interaction between TGF-beta and Wnt signalling components in vivo.