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Development ePress online publication date 3 Nov 2004
doi: 10.1242/dev.01458


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Research article

Stabilization of {beta}-catenin in the mouse zygote leads to premature epithelial-mesenchymal transition in the epiblast


Rolf Kemler*, Andreas Hierholzer, Benoît Kanzler, Stefan Kuppig, Kati Hansen, Makoto M. Taketo, Wilhelmine N. de Vries, Barbara B. Knowles, and Davor Solter
* Author for correspondence (e-mail: kemler{at}immunbio.mpg.de)

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 GSK3{beta}-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 GSK3{beta}-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.


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