Kim C H, Oda T, Itoh M, Jiang D, Artinger K B, Chandrasekharappa S C, Driever W, Chitnis A B
Laboratory of Molecular Genetics, NICHD, NHGRI, NIH, Bethesda, Maryland 20892, USA.
Nature. 2000 Oct 19;407(6806):913-6. doi: 10.1038/35038097.
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.
脊椎动物组织者移植到宿主胚胎腹侧时，凭借其独特的诱导头部和躯干的特性，能够诱导出完整的体轴。组织者分泌的无翅型/翼状螺旋转录因子（Wingless/Wnt）拮抗剂已被鉴定为头部诱导因子。它们的异位表达可促进头部形成，而原肠胚形成早期Wnt信号的异位激活则会阻止头部形成。这些观察结果表明，头部诱导因子在前部结构形成过程中抑制Wnt信号的能力，是它们与允许后部化Wnt信号发挥作用的躯干诱导因子的区别所在。在此，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是由于T细胞因子3（Tcf3）（Tcf/Lef家族成员）发生突变所致。hdl突变体中Tcf3功能的丧失表明，hdl可抑制Wnt靶基因。我们提供了遗传学证据，证明Wnt信号通路的一个组分在脊椎动物头部形成和模式化过程中至关重要。
