PMID:15525667

Citation	Kemler, R, Hierholzer, A, Kanzler, B, Kuppig, S, Hansen, K, Taketo, MM, de Vries, WN, Knowles, BB and Solter, D (2004) Stabilization of beta-catenin in the mouse zygote leads to premature epithelial-mesenchymal transition in the epiblast. Development 131:5817-24
Abstract	Many components of the Wnt/beta-catenin signaling pathway are expressed during mouse pre-implantation embryo development, suggesting that this pathway may control cell proliferation and differentiation at this time. We find no evidence for a functional activity of this pathway in cleavage-stage embryos using the Wnt-reporter line, BAT-gal. To further probe the activity of this pathway, we activated beta-catenin signaling by mating a zona pellucida3-cre (Zp3-cre) transgenic mouse line with a mouse line containing an exon3-floxed beta-catenin allele. The result is expression of a stabilized form of beta-catenin, resistant to degradation by the GSK3beta-mediated proteasome pathway, expressed in the developing oocyte and in each cell of the resulting embryos. Nuclear localization and signaling function of beta-catenin were not observed in cleavage-stage embryos derived from these oocytes. These results indicate that in pre-implantation embryos, molecular mechanisms independent of the GSK3beta-mediated ubiquitination and proteasome degradation pathway inhibit the nuclear function of beta-catenin. Although the mutant blastocysts initially developed normally, they then exhibited a specific phenotype in the embryonic ectoderm layer of early post-implantation embryos. We show a nuclear function of beta-catenin in the mutant epiblast that leads to activation of Wnt/beta-catenin target genes. As a consequence, cells of the embryonic ectoderm change their fate, resulting in a premature epithelial-mesenchymal transition.
Links	PubMed Online version:10.1242/dev.01458
Keywords	Alleles; Animals; Blastocyst/metabolism; Body Patterning; Cell Differentiation; Cell Nucleus/metabolism; Cytoskeletal Proteins/chemistry; Cytoskeletal Proteins/metabolism; Ectoderm/metabolism; Epithelium/metabolism; Exons; Genes, Reporter; Glycogen Synthase Kinase 3/metabolism; Immunohistochemistry; In Situ Hybridization; Lac Operon; Mesoderm/metabolism; Mice; Mice, Inbred C57BL; Mutation; Oocytes/metabolism; Phenotype; Proteasome Endopeptidase Complex/metabolism; Signal Transduction; Time Factors; Trans-Activators/chemistry; Trans-Activators/metabolism; Transgenes; Ubiquitin/metabolism; Zygote/metabolism; beta Catenin; beta-Galactosidase/metabolism
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