GATA-6 maintains BMP-4 and Nkx2 expression during cardiomyocyte precursor maturation.

Journal article

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.

Authors: Peterkin, T; Gibson, A; Patient, R

• Publication status: Published
• Journal: EMBO journal
• Volume: 22
• Issue: 16
• Pages: 4260-4273
• Publication date: 2003-08-01
• DOI: 10.1093/emboj/cdg400
• EISSN: 1460-2075
• ISSN: 0261-4189
• Language: English
• Keywords: Bone Morphogenetic Proteins; Bone Morphogenetic Protein 4; Protein Isoforms; Endoderm; Zinc Fingers; Myocytes, Cardiac; Molecular Sequence Data; Animals; Signal Transduction; Zebrafish; DNA-Binding Proteins; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Cell Differentiation; Transcription Factors; Mesoderm; Base Sequence; GATA6 Transcription Factor; Xenopus; Models, Biological; Zebrafish Proteins; Humans; Homeodomain Proteins; Protein Processing, Post-Translational; Oligonucleotides, Antisense; Xenopus Proteins