title: Differential requirement for the dual functions of β-catenin in embryonic stem cell self-renewal and germ layer formation.
abstract: Canonical Wnt signalling has been implicated in mouse and human embryonic stem cell (ESC) maintenance; however, its requirement is controversial. β-catenin is the key component in this highly conserved Wnt pathway, acting as a transcriptional transactivator. However, β-catenin has additional roles at the plasma membrane regulating cell-cell adhesion, complicating the analyses of cells/tissues lacking β-catenin. We report here the generation of a Ctnnb1 (β-catenin)-deficient mouse ESC (mESC) line and show that self-renewal is maintained in the absence of β-catenin. Cell adhesion is partially rescued by plakoglobin upregulation, but fails to be maintained during differentiation. When differentiated as aggregates, wild-type mESCs form descendants of all three germ layers, whereas mesendodermal germ layer formation and neuronal differentiation are defective in Ctnnb1-deficient mESCs. A Tcf/Lef-signalling-defective β-catenin variant, which re-establishes cadherin-mediated cell adhesion, rescues definitive endoderm and neuroepithelial formation, indicating that the β-catenin cell-adhesion function is more important than its signalling function for these processes.
authors.affiliation: Research Institute of Molecular Pathology, Dr. Bohrgasse 7, 1030 Vienna, Austria.
authors.forename: Natalia
authors.initials: N
authors.lastname: Lyashenko
authors.forename: Markus
authors.initials: M
authors.lastname: Winter
authors.forename: Domenico
authors.initials: D
authors.lastname: Migliorini
authors.forename: Travis
authors.initials: T
authors.lastname: Biechele
authors.forename: Randall T
authors.initials: RT
authors.lastname: Moon
authors.forename: Christine
authors.initials: C
authors.lastname: Hartmann
mesh_terms: D000818:Animals; D001665:Binding Sites; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D051820:TCF Transcription Factors / Q000378:metabolism; D014162:Transfection; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051185:gamma Catenin / Q000378:metabolism
chemical_list: D015415:Biomarkers; C495267:CTNNB1 protein, mouse; C495293:Jup protein, mouse; D051820:TCF Transcription Factors; D051176:beta Catenin; D051185:gamma Catenin