Role of Goosecoid, Xnot and Wnt antagonists in the maintenance of the notochord genetic programme in Xenopus gastrulae.

The Xenopus trunk organiser recruits neighbouring tissues into secondary trunk axial and paraxial structures and itself differentiates into notochord. The inductive properties of the trunk organiser are thought to be mediated by the secretion of bone morphogenetic protein (BMP) antagonists. Ectopic repression of BMP signals on the ventral side is sufficient to mimic the inductive properties of the trunk organiser. Resultant secondary trunks contain somite and neural tube, but no notochord. We show that inhibition of BMP signalling is sufficient for the initiation of the trunk organiser genetic programme at the onset of gastrulation. During late gastrulation, however, this programme is lost, due to an invasion of secreted Wnts from neighbouring tissues. Maintenance of this programme requires co-repression of BMP and Wnt signalling within the presumptive notochord region. To shed light on the molecular cascade that leads to the repression of the Wnt pathway, we looked for individual organiser genes whose overexpression could complement the inhibition of BMP signalling to promote notochord formation in the secondary trunks. Two genes, gsc and Xnot, were thus identified and shown to act in different ways. Xnot acts as a transcriptional repressor within the mesodermal region. Gsc acts in deeper vegetal cells, where it regulates Frzb expression to maintain Xnot expression in the neighbouring notochord territory. These results suggest that, during gastrulation, the necessary repression of Wnt/beta-catenin signalling in notochord precursors is achieved by the action of secreted inhibitors, such as Frzb, emitted by gsc-expressing dorsal vegetal cells.