Regulation of dorsal-ventral axis formation in Xenopus by intercellular and intracellular signalling

The dorsal-ventral axis in the frog, Xenopus laevis, is specified by a microtubule-based process that begins at fertilization. Rotation of the egg cytoplasm leads to the activation of a signalling system on the future dorsal side of the embryo that is responsible for the formation of the Spemann organizer at the dorsal equator. Members of the Wnt family, as well as noggin and activated Vg1, have been shown to mimic this signalling system, but it is not known which factor or factors are used by the embryo. To elucidate this process, we have isolated the Xenopus homologue of the Drosophila zw3/shaggy gene, Xgsk-3, since zw3/shaggy is regulated by the Drosophila Wnt homologue, wingless. We have found that a dominant-negative mutant of Xgsk-3 can induce an ectopic organized when expressed on the ventral side of the Xenopus embryo, leading to embryos with duplicated axes. These results indicate that repression of Xgsk-3 is critical for formation of the dorsal-ventral axis in Xenopus. Inactivation of Xgsk-3 can regulate the fate of neighbouring cells, indicating that the repression of Xgsk-3 may activate a downstream signalling pathway.