GATA-6 maintains BMP-4 and Nkx2 expression during cardiomyocyte precursor maturation.
GATA-6 is expressed in presumptive cardiac mesoderm before gastrulation, but its role in heart development has been unclear. Here we show that Xenopus and zebrafish embryos, injected with antisense morpholino oligonucleotides designed specifically to knock-down translation of GATA-6 protein, are severely compromised for heart development. Injected embryos express greatly reduced levels of contractile machinery genes and, at the same stage, of regulatory genes such as bone morphogenetic protein-4 (BMP-4) and the Nkx2 family. In contrast, initial BMP and Nkx2 expression is normal, suggesting a maintenance role for GATA-6. Endoderm is critical for heart formation in several vertebrates including Xenopus, and separate perturbation of GATA-6 expression in the deep anterior endoderm and in the overlying heart mesoderm shows that GATA-6 is required in both for cardiogenesis. The GATA-6 requirement in cardiac mesoderm was confirmed in zebrafish, an organism in which endoderm is thought not to be necessary for heart formation. We therefore conclude that proper maturation of cardiac mesoderm requires GATA-6, which functions to maintain BMP-4 and Nkx2 expression.
Peterkin
Tessa
T
Institute of Genetics, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Gibson
Abigail
A
Patient
Roger
R
D000818:Animals; D001483:Base Sequence; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000172:deficiency / Q000187:drug effects / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004707:Endoderm / Q000502:physiology; D050993:GATA6 Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008648:Mesoderm / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020033:Protein Isoforms / Q000737:chemistry / Q000172:deficiency / Q000187:drug effects / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000187:drug effects / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000378:metabolism*; D016335:Zinc Fingers
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494758:GATA6 protein, Xenopus; C494759:GATA6 protein, human; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C092720:NKX2-5 protein, Xenopus; C095552:NKX2-5 protein, human; C409765:NKX2-6 protein, Xenopus; C102935:Nkx2.3 protein, zebrafish; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D014157:Transcription Factors; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C525812:bmp4 protein, Xenopus; C525813:bmp4 protein, zebrafish