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- Title
Differential requirement for the dual functions of ?-catenin in embryonic stem cell self-renewal and germ layer formation.
- Authors
Lyashenko, Natalia; Winter, Markus; Migliorini, Domenico; Biechele, Travis; Moon, Randall T.; Hartmann, Christine
- Abstract
Canonical Wnt signalling has been implicated in mouse and human embryonic stem cell (ESC) maintenance; however, its requirement is controversial. ?-catenin is the key component in this highly conserved Wnt pathway, acting as a transcriptional transactivator. However, ?-catenin has additional roles at the plasma membrane regulating cell-cell adhesion, complicating the analyses of cells/tissues lacking ?-catenin. We report here the generation of a Ctnnb1 (?-catenin)-deficient mouse ESC (mESC) line and show that self-renewal is maintained in the absence of ?-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 ?-catenin variant, which re-establishes cadherin-mediated cell adhesion, rescues definitive endoderm and neuroepithelial formation, indicating that the ?-catenin cell-adhesion function is more important than its signalling function for these processes.
- Subjects
EMBRYONIC stem cells; GERM cells; CELL membranes; CELL adhesion; CELL differentiation; LABORATORY mice
- Publication
Nature Cell Biology, 2011, Vol 13, Issue 7, p753
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb2260