Formation of Multiple Hearts in Mice following Deletion of β-catenin in the Embryonic Endoderm

Abstract

Using Cre/loxP, we conditionally inactivated the beta-catenin gene in cells of structures that exhibit important embryonic organizer functions: the visceral endoderm, the node, the notochord, and the definitive endoderm. Mesoderm formation was not affected in the mutant embryos, but the node was missing, patterning of the head and trunk was affected, and no notochord or somites were formed. Surprisingly, deletion of beta-catenin in the definitive endoderm led to the formation of multiple hearts all along the anterior-posterior (A/P) axis of the embryo. Ectopic hearts developed in parallel with the normal heart in regions of ectopic Bmp2 expression. We provide evidence that ablation of beta-catenin in embryonic endoderm changes cell fate from endoderm to precardiac mesoderm, consistent with the existence of bipotential mesendodermal progenitors in mouse embryos.

Induction and Down-regulation of Sox17 and Its Possible Roles During the Course of Gastrointestinal Tumorigenesis

“…Moreover, it has been shown that β-catenin is also essential for definitive endoderm formation 36 . We demonstrate here that Sox17 continuously expresses in the stomach and intestine during organogenesis.…”

Cardiac-specific haploinsufficiency of β-catenin attenuates cardiac hypertrophy but enhances fetal gene expression in response to aortic constriction

“…Thus deletion of β-catenin in the endoderm promotes cardiac differentiation leading to ectopic heart formation [26]. Activation of β-catenin signaling, however, is required for in vitro cardiac myogenesis and differentiation [27].…”

The β-Catenin/T-Cell Factor/Lymphocyte Enhancer Factor Signaling Pathway Is Required for Normal and Stress-Induced Cardiac Hypertrophy

“…An additional control was WT/Cre. Genotyping was performed with PCR using specific primers as described previously (7,33,54). Mer-Cre-Mer expression levels, determined by immunoblotting with an anti-Cre antibody, were equal in the ␤-catenin fl/fl /Cre versus WT/Cre mice (data not shown).…”

“…The breeding scheme for conditional deletion of ␤-catenin involved crossing the ␤-catenin fl/fl mouse obtained from Jackson Laboratories (7,33) with the heterozygous Mer-Cre-Mer mouse. The latter expresses Cre flanked by two modified estrogen receptors that are responsive to tamoxifen (54).…”

“…Since mice deleted for ␤-catenin have multiple ectopic hearts (33), the pathway appears to antagonize cardiomyocyte differentiation and/or to restrict the size of the cardiogenic field (15). In addition, later in development, the pathway, acting in part via Pitx2, a member of the bicoid family of transcription factors, is critical for cushion morphogenesis, outflow tract development, and valve formation (26,27).…”