A role for Xenopus Frizzled 8 in dorsal development

The establishment of cell and tissue polarity during animal development often requires signaling by Wnts, extracellular signaling polypeptides. Transmembrane receptors of the Frizzled family are implicated in the transduction of Wnt signals in responding cells. Xfz8 is a novel cDNA encoding a Xenopus homologue of mouse Frizzled 8. Xfz8 transcripts are expressed zygotically in the organizer at the early gastrula stage and in the most anterior ectoderm at later stages, suggesting a role in axis specification. When Xfz8 mRNA is overexpressed in ventral marginal zone cells, a secondary body axis with prominent head structures develops. Surprisingly, axis induction was not accompanied by activation of early dorsal marginal zone markers at the gastrula stages, whereas Xwnt8 induced these markers with high efficiency. These findings suggest that Xfz8 is a product of the organizer and mimics its function. Head induction by Xfz8 was blocked by co-expression of GSK3beta or a dominant negative form of Xenopus Dishevelled, suggesting that this effect of Xfz8 requires Wnt signal transduction. When Xfz8 is overexpressed in animal pole cells, dorsal marginal zone markers Xnr3, Xotx2 and a promoter construct for Siamois, were selectively activated, demonstrating the difference in competence between animal pole cells and ventral marginal zone cells in response to Xfz8. It is proposed that the Wnt pathways are activated at two different steps during axis formation: to induce the Spemann organizer and to implement organizer functions by triggering dorsoanterior development.