Zygotic Wnt activity is required for Brachyury expression in the early Xenopus laevis embryo.
Zygotic Wnt activity is required for Brachyury expression in the early Xenopus laevis embryo.
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DOI：
10.1006/dbio.2002.0786
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发表时间：
2002-10
影响因子：
2.7
通讯作者：
A. Vonica;B. Gumbiner
中科院分区：
文献类型：
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作者：
A. Vonica;B. Gumbiner
典型的、β-连环蛋白依赖性 Wnt 通路在非洲爪蟾发育的早期事件中发挥着至关重要的作用。背轴形成和中胚层模式形成是该途径公认的作用，但参与中胚层规范的基因表达的调节则不然。这一结论主要是基于 Wnt 途径无法在动物帽外植体中诱导中胚层。通过注射经典 Wnt 信号传导抑制剂，我们证明一般中胚层标记 Brachyury (Xbra) 的表达需要整个边缘区的合子、配体依赖性 Wnt 活性。对 Xbra 启动子的分析表明，推定的 TCF 结合位点介导 Wnt 激活，这是这个经过充分研究的启动子中第一个可归因于激活作用的位点。然而，已建立的中胚层诱导剂（如 eFGF 和激活素）可以绕过 Xbra 表达的 Wnt 要求。另一种中胚层促进因子 VegT 以 Wnt 依赖性方式激活 Xbra。我们还表明，激活素/节点信号传导对于 Wnt 途径（而非 VegT）异位 Xbra 诱导是必需的。我们的数据显着改变了对非洲爪蟾 Brachyury 调控的理解，这意味着斯佩曼组织体中存在未知的合子 Wnt 配体。由于 Brachyury 被认为在中胚层形成中起主要作用，因此除了模式形成之外，Wnt 可能在中胚层规范中发挥作用。
The canonical, beta-catenin-dependent Wnt pathway is a crucial player in the early events of Xenopus development. Dorsal axis formation and mesoderm patterning are accepted effects of this pathway, but the regulation of expression of genes involved in mesoderm specification is not. This conclusion is based largely on the inability of the Wnt pathway to induce mesoderm in animal cap explants. Using injections of inhibitors of canonical Wnt signaling, we demonstrate that expression of the general mesodermal marker Brachyury (Xbra) requires a zygotic, ligand-dependent Wnt activity throughout the marginal zone. Analysis of the Xbra promoter reveals that putative TCF-binding sites mediate Wnt activation, the first sites in this well-studied promoter to which an activation role can be ascribed. However, established mesoderm inducers like eFGF and activin can bypass the Wnt requirement for Xbra expression. Another mesoderm promoting factor, VegT, activates Xbra in a Wnt-dependent manner. We also show that the activin/nodal signaling is necessary for ectopic Xbra induction by the Wnt pathway, but not by VegT. Our data significantly change the understanding of Brachyury regulation in Xenopus, implying the existence of an unknown zygotic Wnt ligand in Spemann's organizer. Since Brachyury is considered to have a major role in mesoderm formation, it is possible that Wnts might play a role in mesoderm specification, in addition to patterning.