Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A

Abstract Wnt genes encode secreted proteins which are implicated in receptor-mediated cell–cell signaling events important in embryogenesis, but the second messenger systems modulated by Wnts have not been identified. We report that ectopic expression of Xwnt -5A in zebrafish embryos enhances the frequency of intracellular Ca 2+ transients in the enveloping layer of the blastodisc, whereas Xwnt -8 does not. These transients are independent of extracellular Ca 2+ . Consistent with the observed Ca 2+ transients playing a role in responses of embryos to Xwnt -5A, we report that the ligand-activated serotonin type 1C receptor, which stimulates PI cycle activity and Ca 2+ signaling independent of Wnts, phenocopies embryonic responses to Xwnt -5A. These results suggest that intercellular signaling by a subset of vertebrate Wnts involves modulation of a intracellular Ca 2+ signaling pathway, which may arise from phosphatidylinositol cycle activity.