ESTABLISHMENT OF THE DORSOVENTRAL AXIS IN XENOPUS EMBRYOS IS PRESAGEDBY EARLY ASYMMETRIES IN BETA-CATENIN THAT ARE MODULATED BY THE WNT SIGNALING PATHWAY

Eggs of Xenopus laevis undergo a postfertilization cortical rotation t hat specifies the position of the dorso-ventral axis and activates a t ransplantable dorsal-determining activity in dorsal blastomeres by the 32-cell stage. There have heretofore been no reported dorso-ventral a symmetries in endogenous signaling proteins that may be involved in th is dorsal-determining activity during early cleavage stages. We focuse d on beta-catenin as a candidate for an asymmetrically localized dorsa l-determining factor since it is both necessary and sufficient for dor sal axis formation. We report that beta-catenin displays greater cytop lasmic accumulation on the future dorsal side of the Xenopus embryo by the two-cell stage. This asymmetry persists and increases through ear ly cleavage stages, with beta-catenin accumulating in dorsal but not v entral nuclei by the 16- to 32-cell stages. We then investigated which potential signaling factors and pathways are capable of modulating th e steady-state levels of endogenous beta-catenin. Steady-state levels and nuclear accumulation of beta-catenin increased in response to ecto pic Xenopus Wnt-8 (Xwnt-8) and to the inhibition of glycogen synthase kinase-3, whereas neither Xwnt-5A, BVg1, nor noggin increased beta-cat enin levels before the mid-blastula stage. As greater levels and nucle ar accumulation of beta-catenin on the future dorsal side of the embry o correlate with the induction of specific dorsal genes, our data sugg est that early asymmetries in beta-catenin presage and may specify dor so-ventral differences in gene expression and cell fate. Our data furt her support the hypothesis that these dorso-ventral differences in bet a-catenin arise in response to the postfertilization activation of a s ignaling pathway that involves Xenopus glycogen synthase kinase-3.