Repressor activity of headless/Tcf3 is essential for vertebrate head formation

The vertebrate organizer can induce a complete body axis when transplanted to the ventral side of a host embryo(1) by virtue of its distinct head and trunk inducing properties. Wingless/Wnt antagonists secreted by the organiz er have been identified as head inducers(2-4). Their ectopic expression can promote head formation, whereas ectopic activation of Wnt signalling durin g early gastrulation blocks head formation(5-7). These observations suggest that the ability of head inducers to inhibit Wnt signalling during formati on of anterior structures is what distinguishes them from trunk inducers th at permit the operation of posteriorizing Wnt signals(8). Here we describe the zebrarsh headless (hdl) mutant and show that its severe head defects ar e due to a mutation in T-cell factor-3 (Tcf3), a member of the Tcf/Lef fami ly(9,10). Loss of Tcf3 function in the hdl mutant reveals that hdl represse s Wnt target genes. We provide genetic evidence that a component of the Wnt signalling pathway is essential in vertebrate head formation and patternin g.