The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos

Abstract

It is thought that inositol-1,4,5-trisphosphate (Ins(1,4,5)P₃)-Ca²⁺ signalling has a function in dorsoventral axis formation in Xenopus embryos^1,2,3; however, the immediate target of free Ca²⁺ is unclear. The secreted Wnt protein family comprises two functional groups, the canonical Wnt and Wnt/Ca²⁺ pathways⁴. The Wnt/Ca²⁺ pathway interferes with the canonical Wnt pathway⁵, but the underlying molecular mechanism is poorly understood. Here, we cloned the complementary DNA coding for the Xenopus homologue of nuclear factor of activated T cells (XNF-AT). A gain-of-function, calcineurin-independent active XNF-AT mutation (CA XNF-AT) inhibited anterior development of the primary axis, as well as Xwnt-8-induced ectopic dorsal axis development in embryos. A loss-of-function, dominant negative XNF-AT mutation (DN XNF-AT) induced ectopic dorsal axis formation and expression of the canonical Wnt signalling target molecules siamois and Xnr3 (ref. 4). Xwnt-5A induced translocation of XNF-AT from the cytosol to the nucleus. These data indicate that XNF-AT functions as a downstream target of the Wnt/Ca²⁺ and Ins(1,4,5)P₃-Ca²⁺ pathways, and has an essential role in mediating ventral signals in the Xenopus embryo through suppression of the canonical Wnt pathway.