Dorsal downregulation of GSK3 beta by a non-Wnt-like mechanism is an earlymolecular consequence of cortical rotation in early Xenopus embryos

Cortical rotation and concomitant dorsal translocation of cytoplasmic deter minants are the earliest events known to be necessary for dorsoventral patt erning in Xenopus embryos. The earliest known molecular target is beta-cate nin, which is essential for dorsal development and becomes dorsally enriche d shortly after cortical rotation. In mammalian cells cytoplasmic accumulat ion of beta-catenin follows reduction of the specific activity of glycogen synthase kinase 3-beta (GSK3 beta), In Xenopus embryos, exogenous GSK3 beta suppresses dorsal development as predicted and GSK3 beta dominant negative (kinase dead) mutants cause ectopic axis formation. However, endogenous GS K3 beta regulation is poorly characterized. Here we demonstrate two modes o f GSK3 beta regulation in Xenopus. Endogenous mechanisms cause depletion of GSK3 beta protein on the dorsal side of the embryo. The timing, location a nd magnitude of the depletion correspond to those of endogenous beta-cateni n accumulation. uv and D2O treatments that abolish and enhance dorsal chara cter of the embryo, respectively, correspondingly abolish and regulator of GSK3 beta, GSK3-binding protein (GBP), known to be essential for axis forma tion, also induces depletion of GSK3 beta, Depletion of GSK3 beta is a prev iously undescribed mode of regulation of this signal transducer. The other mode of regulation is observed in response to Wnt and dishevelled expressio n. Neither Wnt nor dishevelled causes depletion but instead they reduce GSK 3 beta-specific activity. Thus, Wnt/Dsh and GBP appear to effect two bioche mically distinct modes of GSK3 beta regulation.