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Journal Article

Differential requirements for β-catenin during mouse development


Rudloff,  Stefan
Max Planck Society;


Kemler,  Rolf
Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Rudloff, S., & Kemler, R. (2012). Differential requirements for β-catenin during mouse development. Development and Stem Cells, 139, 3711-3721.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-8D5B-3
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% (ROSA26β/+) or ~25% (ROSA26β/β) of wild-type levels. ROSA26β/+ 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 ROSA26β/β ES cells. We conclude that even very low β-catenin levels are able to sustain cell adhesion, but not Wnt signaling. During development, ROSA26β/β as well as ROSA26β/+ 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 ROSA26β/+ or ROSA26β/β 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.