The Fate of Wnt Signaling

Abstract

The Wnt family of secreted proteins regulates various cellular processes through cell surface receptors of the Frizzled family. The best understood canonical Wnt-Frizzled pathway induces the translocation of cytosolic β-catenin to the nucleus to regulate gene expression. However, less is known about an alternative non-canonical Wnt pathway that involves an increase in intracellular calcium. Saneyoshi et al. demonstrate that in early Xenopus embryos, a transcription factor previously implicated in immune cell regulation called nuclear factor of activated T cells (NF-AT), is activated by the Wnt-calcium pathway. Activation of this noncanonical pathway caused translocation of NF-AT to the nucleus in embryonic cells. Inhibition of this pathway perturbed cell movement during gastrulation, altering ventral side formation by promoting a dorsal fate instead. NF-AT was also dephosphorylated by the phosphastase calcineurin in response to a rise in intracellular calcium. By showing that NFAT inhibits the canonical Wnt pathway upstream of β-catenin, the authors suggest that cross talk between the two Wnt signaling cascades may be necessary for establishing dorsal-ventral polarity of the developing embryo. T. Saneyoshi, S. Kume, Y. Amasaki, K. Mikoshiba, The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature 417 , 295-299 (2002). [Online Journal]