First Author | Lyashenko N | Year | 2011 |
Journal | Nat Cell Biol | Volume | 13 |
Issue | 7 | Pages | 753-61 |
PubMed ID | 21685890 | Mgi Jnum | J:174452 |
Mgi Id | MGI:5086053 | Doi | 10.1038/ncb2260 |
Citation | Lyashenko N, et al. (2011) Differential requirement for the dual functions of beta-catenin in embryonic stem cell self-renewal and germ layer formation. Nat Cell Biol 13(7):753-61 |
abstractText | Canonical Wnt signalling has been implicated in mouse and human embryonic stem cell (ESC) maintenance; however, its requirement is controversial. beta-catenin is the key component in this highly conserved Wnt pathway, acting as a transcriptional transactivator. However, beta-catenin has additional roles at the plasma membrane regulating cell-cell adhesion, complicating the analyses of cells/tissues lacking beta-catenin. We report here the generation of a Ctnnb1 (beta-catenin)-deficient mouse ESC (mESC) line and show that self-renewal is maintained in the absence of beta-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 beta-catenin variant, which re-establishes cadherin-mediated cell adhesion, rescues definitive endoderm and neuroepithelial formation, indicating that the beta-catenin cell-adhesion function is more important than its signalling function for these processes. |