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

Nat Cell Biol. 2011 Jun 19;13(7):753-61. doi: 10.1038/ncb2260.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Biomarkers / metabolism
  • Cell Adhesion
  • Cell Differentiation
  • Cell Line
  • Cell Movement* / genetics
  • Cell Proliferation*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Mice
  • Mice, Knockout
  • Morphogenesis
  • Neurons / metabolism
  • Promoter Regions, Genetic
  • RNA Interference
  • Signal Transduction* / genetics
  • TCF Transcription Factors / metabolism
  • Transfection
  • beta Catenin / deficiency
  • beta Catenin / genetics
  • beta Catenin / metabolism*
  • gamma Catenin / metabolism


  • Biomarkers
  • CTNNB1 protein, mouse
  • Jup protein, mouse
  • TCF Transcription Factors
  • beta Catenin
  • gamma Catenin