title: Dishevelled proteins regulate cell adhesion in mouse blastocyst and serve to monitor changes in Wnt signaling.
abstract: Wnt signaling is essential for the regulation of cell polarity and cell fate in the early embryogenesis of many animal species. Multiple Wnt genes and its pathway members are expressed in the mouse early embryo, raising the question whether they play any roles in preimplantation development. Dishevelled is an important transducer of divergent Wnt pathways. Here we show that three of the mouse Dishevelled proteins are not only expressed in oocytes and during preimplantation development, but also display distinct spatio-temporal localization. Interestingly, as embryos reach blastocyst stage, Dishevelled 2 becomes increasingly associated with cell membrane in trophectoderm cells, while at E4.5, Dishevelled 3 is highly enriched in the cytoplasm of ICM cells. These changes are coincident with an increase in the active form of beta-catenin, p120catenin transcription and decrease of Kaiso expression, indicating an upregulation of Wnt signaling activity before implantation. When Dishevelled-GFP fusion proteins are overexpressed in single blastomeres of the 4-cell stage embryo, the progeny of this cell show reduction in cell adhesiveness and a rounded shape at the blastocyst stage. This suggests that perturbing Dvl function interferes with cell-cell adhesion through the non-canonical Wnt pathway in blastocysts.
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology and Department of Genetics, University of Cambridge, Cambridge, UK.
authors.forename: Jie
authors.initials: J
authors.lastname: Na
authors.forename: Karin
authors.initials: K
authors.lastname: Lykke-Andersen
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Torres Padilla
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zernicka-Goetz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D000072261:Dishevelled Proteins; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C495267:CTNNB1 protein, mouse; D051177:Catenins; D015815:Cell Adhesion Molecules; D000072261:Dishevelled Proteins; C000606582:Dvl2 protein, mouse; C000606585:Dvl3 protein, mouse; D010750:Phosphoproteins; D014157:Transcription Factors; D051153:Wnt Proteins; C118822:Zbtb33 protein, mouse; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D000095002:Delta Catenin