| First Author | Rudloff S | Year | 2012 |
| Journal | Development | Volume | 139 |
| Issue | 20 | Pages | 3711-21 |
| PubMed ID | 22991437 | Mgi Jnum | J:187739 |
| Mgi Id | MGI:5438141 | Doi | 10.1242/dev.085597 |
| Citation | Rudloff S, et al. (2012) Differential requirements for beta-catenin during mouse development. Development 139(20):3711-21 |
| abstractText | Embryogenesis relies on the precise interplay of signaling cascades to activate tissue-specific differentiation programs. An important player in these morphogenetic processes is beta-catenin, which is a central component of adherens junctions and canonical Wnt signaling. Lack of beta-catenin is lethal before gastrulation, but mice heterozygous for beta-catenin (Ctnnb1) develop as wild type. Here, we confine beta-catenin amounts below the heterozygous expression level to study the functional consequences for development. We generate embryonic stem (ES) cells and embryos expressing beta-catenin only from the ubiquitously active ROSA26 promoter and thereby limit beta-catenin expression to ~12.5% (ROSA26(beta/+)) or ~25% (ROSA26(beta/beta)) of wild-type levels. ROSA26(beta/+) 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(beta/beta) ES cells. We conclude that even very low beta-catenin levels are able to sustain cell adhesion, but not Wnt signaling. During development, ROSA26(beta/beta) as well as ROSA26(beta/+) 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 beta-catenin levels. Strikingly, if ROSA26(beta/+) or ROSA26(beta/beta) is first activated after gastrulation, subsequent development correlates with the dosage of beta-catenin. Moreover, molecular evidence indicates that the amount of beta-catenin controls the induction of specific Wnt target genes. In conclusion, by restricting its expression we determine the level of beta-catenin required for adhesion or pluripotency and during different morphogenetic events. |
