Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/β-catenin activity

We provide genetic evidence defining a role for noncanonical Wnt function in vertebrate axis formation. In zebrafish, misexpression of Wnt-4, -5, and -11 stimulates calcium (Ca(2+)) release, defining the Wnt/Ca(2+) class. We describe genetic interaction between two Wnt/Ca(2+) members, Wnt-5 (pipetail) and Wnt-11 (silberblick), and a reduction of Ca(2+) release in Wnt-5/pipetail. Embryos genetically depleted of both maternal and zygotic Wnt-5 product exhibit cell movement defects as well as hyperdorsalization and axis-duplication phenotypes. The dorsalized phenotypes result from increased β-catenin accumulation and activation of downstream genes. The Wnt-5 loss-of-function defect is consistent with Ca(2+) modulation having an antagonistic interaction with Wnt/β-catenin signaling.