Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm.
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.
Department of Molecular Embryology, Max-Planck Institute for Immunobiology, Stuebeweg 51, D-79108 Freiburg, Germany.
Heiko
H
Lickert
Stefanie
S
Kutsch
Benoît
B
Kanzler
Yoshitaka
Y
Tamai
Makoto M
MM
Taketo
Rolf
R
Kemler
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D002678:Chimera / Q000002:abnormalities / Q000235:genetics / Q000378:metabolism; D002828:Choristoma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D005260:Female; D050991:GATA4 Transcription Factor; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006257:Head / Q000002:abnormalities; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000002:abnormalities* / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; C110586:Cer1 protein, mouse; D016207:Cytokines; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C501127:Dkk1 protein, mouse; D050991:GATA4 Transcription Factor; C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin