title: Establishment of the dorso-ventral axis in Xenopus embryos is presaged by early asymmetries in beta-catenin that are modulated by the Wnt signaling pathway.
abstract: Eggs of Xenopus laevis undergo a postfertilization cortical rotation that specifies the position of the dorso-ventral axis and activates a transplantable dorsal-determining activity in dorsal blastomeres by the 32-cell stage. There have heretofore been no reported dorso-ventral asymmetries in endogenous signaling proteins that may be involved in this dorsal-determining activity during early cleavage stages. We focused on beta-catenin as a candidate for an asymmetrically localized dorsal-determining factor since it is both necessary and sufficient for dorsal axis formation. We report that beta-catenin displays greater cytoplasmic accumulation on the future dorsal side of the Xenopus embryo by the two-cell stage. This asymmetry persists and increases through early cleavage stages, with beta-catenin accumulating in dorsal but not ventral nuclei by the 16- to 32-cell stages. We then investigated which potential signaling factors and pathways are capable of modulating the steady-state levels of endogenous beta-catenin. Steady-state levels and nuclear accumulation of beta-catenin increased in response to ectopic Xenopus Wnt-8 (Xwnt-8) and to the inhibition of glycogen synthase kinase-3, whereas neither Xwnt-5A, BVg1, nor noggin increased beta-catenin levels before the mid-blastula stage. As greater levels and nuclear accumulation of beta-catenin on the future dorsal side of the embryo correlate with the induction of specific dorsal genes, our data suggest that early asymmetries in beta-catenin presage and may specify dorso-ventral differences in gene expression and cell fate. Our data further support the hypothesis that these dorso-ventral differences in beta-catenin arise in response to the postfertilization activation of a signaling pathway that involves Xenopus glycogen synthase kinase-3.
authors.affiliation: Lawrence Berkeley National Laboratory, University of California at Berkeley, 94720, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Larabell
authors.forename: M
authors.initials: M
authors.lastname: Torres
authors.forename: B A
authors.initials: BA
authors.lastname: Rowning
authors.forename: C
authors.initials: C
authors.lastname: Yost
authors.forename: J R
authors.initials: JR
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.forename: D
authors.initials: D
authors.lastname: Kimelman
authors.forename: R T
authors.initials: RT
authors.lastname: Moon
mesh_terms: D000818:Animals; D019521:Body Patterning; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006023:Glycoproteins / Q000502:physiology; D018021:Lithium Chloride / Q000494:pharmacology; D011506:Proteins / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014466:Ultraviolet Rays; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology; D029961:Zebrafish Proteins; D051176:beta Catenin; D000099176:Noggin Protein
chemical_list: D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006023:Glycoproteins; D018021:Lithium Chloride; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000099176:Noggin Protein; C495266:CTNNB1 protein, Xenopus; C513103:GDF1 protein, Xenopus; C085096:Wnt5a protein, Xenopus; C094521:wnt8a protein, zebrafish