Nishita M, Hashimoto M K, Ogata S, Laurent M N, Ueno N, Shibuya H, Cho K W
Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Japan.
Nature. 2000 Feb 17;403(6771):781-5. doi: 10.1038/35001602.
Members of the Wnt and TGF-beta superfamilies regulate both cell fate and proliferation during development and tissue maintenance. 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. 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.
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。在早期两栖动物胚胎中，Wnt和TGF-β超家族信号级联对于背侧信号中心（施佩曼组织者）的建立是必需的。两条信号通路的细胞内蛋白在激活后会转移到细胞核中参与转录。在这里，我们表明，作为Wnt信号级联下游成分的β-连环蛋白和Lef1/Tcf，与Smad4形成复合物，Smad4是TGF-β生长因子超家族成员启动信号的重要介质。在非洲爪蟾中，这种相互作用在组织者形成过程中直接且协同地影响双（Xtwn）基因的表达。据我们所知，这是体内TGF-β和Wnt信号成分之间物理相互作用的首次证明。
