Skip to main content
Article thumbnail
Location of Repository

Differential requirements for β-catenin during mouse development

By S. Rudloff and R. Kemler


Embryogenesis relies on the precise interplay of signaling cascades to activate tissue-specific differentiation programs. An important player in these morphogenetic processes is β-catenin, which is a central component of adherens junctions and canonical Wnt signaling. Lack of β-catenin is lethal before gastrulation, but mice heterozygous for β-catenin (Ctnnb1) develop as wild type. Here, we confine β-catenin amounts below the heterozygous expression level to study the functional consequences for development. We generate embryonic stem (ES) cells and embryos expressing β-catenin only from the ubiquitously active ROSA26 promoter and thereby limit β-catenin expression to ~12.5% (ROSA26<sup>β/+</sup>) or ~25% (ROSA26<sup>β/β</sup>) of wild-type levels. ROSA26<sup>β/+</sup> is sufficient to maintain ES cell morphology and pluripotent characteristics, but is insufficient to activate canonical target genes upon Wnt stimulation. This Wnt signaling deficiency is incompletely restored in ROSA26<sup>β/β</sup> ES cells. We conclude that even very low β-catenin levels are able to sustain cell adhesion, but not Wnt signaling. During development, ROSA26<sup>β/β</sup> as well as ROSA26<sup>β/+</sup> partially rescues the knockout phenotype, yet proper gastrulation is absent. These embryos differentiate according to the neural default hypothesis, indicating that gastrulation depends on high β-catenin levels. Strikingly, if ROSA26<sup>β/+</sup> or ROSA26<sup>β/β</sup> is first activated after gastrulation, subsequent development correlates with the dosage of β-catenin. Moreover, molecular evidence indicates that the amount of β-catenin controls the induction of specific Wnt target genes. In conclusion, by restricting its expression we determine the level of β-catenin required for adhesion or pluripotency and during different morphogenetic events

Year: 2012
OAI identifier:
Provided by: MPG.PuRe
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • (external link)
  • Suggested articles

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.