Wnt separate ways, met later

Members of the Wnt family of secreted signaling proteins control a wide range of developmental and pathological processes, with each Wnt protein signaling through either the “canonical” or “noncanonical” pathway. Two papers in this issue (and a Comment on page 753) now bring these two pathways together, showing that the noncanonical can directly antagonize the canonical to regulate signals critical for vertebrate body axis determination, limb development, and possibly oncogenesis.

The canonical Wnt pathway stabilizes the signaling protein β-catenin against degradation, whereas the noncanonical pathway has been considered largely β-catenin independent, operating instead through a network of calcium-dependent intermediates.

Westfall et al. (page 889) identified the noncanonical Wnt family members in zebrafish and found that a loss of function in one of them, Wnt-5, leads to an increase in β-catenin activity and...