Role of IP_3 receptor/ Ca^<2+> signaling for synaptic plasticity and development and differentiation of brain

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The involvement of IP_3-Ca^<2+> signaling in dorsoventral axis formation in Xenopus embryo has been proposed, but the immediate target of free Ca^<2+> is not well understood. The secreted Wnt protein family comprises two functional groups, canonical Wnt and Wnt/Ca^<2+> pathways. Despite the finding that the Wnt/Ca^<2+> pathway interfered with the canonical Wnt pathway, the underlying molecular mechanism is poorly understood. We cloned the cDNA encoding Xenopus homolog of the nuclear factor of activated T-cell (XNF-AT). Gain-of-function XNF-AT mutant (CA XNF-AT) inhibited anterior development of the primary axis as well as Xwnt8-induced ectopic dorsal axis. Loss-of-function XNF-AT mutant (DN XNF-AT) induced an ectopic dorsal axis and expression of the canonical Wnt signaling target molecules, siamois and Xnr3. Xwnt5A induced translocation of XNF-AT from the cytosol to the nucleus. These data strongly suggest that XNF-AT functions as a downstream target of Wnt/Ca^<2+> and IP_3-Ca^<2+> pathways and plays an essential role in mediating ventral signals in the Xenopus embryo by suppressing the canonical Wnt pathway.