The vertebrate organizer can induce a complete body axis when transplanted to the ventral side of a host embryo by virtue of its distinct head and trunk inducing properties. Wingless/Wnt antagonists secreted by the organizer have been identified as head inducers. Their ectopic expression can promote head formation, whereas ectopic activation of Wnt signalling during early gastrulation blocks head formation. These observations suggest that the ability of head inducers to inhibit Wnt signalling during formation of anterior structures is what distinguishes them from trunk inducers that permit the operation of posteriorizing Wnt signals. Here we describe the zebrafish headless (hdl) mutant and show that its severe head defects are due to a mutation in T-cell factor-3 (Tcf3), a member of the Tcf/Lef family. Loss of Tcf3 function in the hdl mutant reveals that hdl represses Wnt target genes. We provide genetic evidence that a component of the Wnt signalling pathway is essential in vertebrate head formation and patterning.

译文

:脊椎动物的组织者因其独特的头和躯干诱导特性,在移植到宿主胚胎的腹侧时可以诱导完整的体轴。组织者分泌的无翅/ Wnt拮抗剂已被确定为头诱导剂。它们的异位表达可以促进头的形成,而早期胃泌尿过程中Wnt信号的异位激活会阻止头的形成。这些观察结果表明,头部诱导物在前部结构形成过程中抑制Wnt信号的能力是它们与躯干诱导剂的区别,躯干诱导剂允许后向性Wnt信号的运作。在这里,我们描述了斑马鱼无头(hdl)突变体,并表明其严重的头部缺陷归因于Tcf / Lef家族成员T细胞因子3(Tcf3)的突变。 hdl突变体中Tcf3功能的丧失揭示了hdl抑制Wnt靶基因。我们提供遗传证据,Wnt信号通路的一个组成部分在脊椎动物头部的形成和模式中是必不可少的。

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