Hsieh J C, Kodjabachian L, Rebbert M L, Rattner A, Smallwood P M, Samos C H, Nusse R, Dawid I B, Nathans J
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature. 1999 Apr 1;398(6726):431-6. doi: 10.1038/18899.
The Wnt proteins constitute a large family of extracellular signalling molecules that are found throughout the animal kingdom and are important for a wide variety of normal and pathological developmental processes. Here we describe Wnt-inhibitory factor-1 (WIF-1), a secreted protein that binds to Wnt proteins and inhibits their activities. WIF-1 is present in fish, amphibia and mammals, and is expressed during Xenopus and zebrafish development in a complex pattern that includes paraxial presomitic mesoderm, notochord, branchial arches and neural crest derivatives. We use Xenopus embryos to show that WIF-1 overexpression affects somitogenesis (the generation of trunk mesoderm segments), in agreement with its normal expression in paraxial mesoderm. In vitro, WIF-1 binds to Drosophila Wingless and Xenopus Wnt8 produced by Drosophila S2 cells. Together with earlier results obtained with the secreted Frizzled-related proteins, our results indicate that Wnt proteins interact with structurally diverse extracellular inhibitors, presumably to fine-tune the spatial and temporal patterns of Wnt activity.
Wnt蛋白构成了一个庞大的细胞外信号分子家族，在整个动物界都能找到，并且对多种正常和病理发育过程都很重要。在此，我们描述了Wnt抑制因子1（WIF-1），一种与Wnt蛋白结合并抑制其活性的分泌蛋白。WIF-1存在于鱼类、两栖动物和哺乳动物中，在非洲爪蟾和斑马鱼发育过程中以复杂的模式表达，包括轴旁体节中胚层、脊索、鳃弓和神经嵴衍生物。我们利用非洲爪蟾胚胎表明，WIF-1的过表达会影响体节发生（躯干中胚层节段的产生），这与其在轴旁中胚层中的正常表达一致。在体外，WIF-1与果蝇S2细胞产生的果蝇无翅蛋白和非洲爪蟾Wnt8结合。与之前关于分泌型卷曲相关蛋白的研究结果一起，我们的结果表明，Wnt蛋白与结构多样的细胞外抑制剂相互作用，推测是为了微调Wnt活性的时空模式。
