Differential requirement for the dual functions of β-catenin in embryonic stem cell self-renewal and

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. Canonical Wnt signalling and its transcriptional effector β-catenin have been implicated in embryonic stem cell (ESC) function. Self-renewal is now shown to be maintained in β-catenin-deficient mouse ESCs, whereas mesendodermal and neuronal differentiation are impaired. A β-catenin variant that cannot function in transcription but re-establishes cadherin-mediated cell-adhesion rescues these differentiation defects.

Cite this article

Lyashenko, N., Winter, M., Migliorini, D. et al. Differential requirement for the dual functions of β-catenin in embryonic stem cell self-renewal and germ layer formation. Nat Cell Biol 13, 753–761 (2011). https://doi.org/10.1038/ncb2260

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