Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
A functioning heart muscle is required continuously throughout life. During embryonic development the heart muscle tissue differentiates from mesoderm that has heart-forming potential. Heart-forming potential in the embryonic mesoderm is regulated by pro-cardiogenic transcription factors, such as members of the GATA and NK-2 transcription factor families. Subsequent heart muscle differentiation involves the expression of cytoskeletal proteins, including myosins and troponins. Different Wnt signalling pathways have various functions in heart development. So-called 'canonical' (Wnt/beta-catenin-mediated) signalling has a conserved role in vertebrate heart development, regulating and restricting heart development and subsequent heart muscle differentiation. Here we investigated the way in which Wnt/beta-catenin signalling functionally interacts with the GATA family of pro-cardiogenic transcription factors to regulate subsequent heart muscle differentiation. We used whole Xenopus embryos as an accessible experimental model system for vertebrate heart development. Our experiments confirmed that activation of Wnt signalling results in reduced gata gene expression, as well as reduced gene expression of other pro-cardiogenic transcription factors and heart muscle differentiation markers. Remarkably, we discovered that when GATA function is experimentally restored, the expression of other pro-cardiogenic transcription factors and heart muscle differentiation markers is rescued. These findings, obtained from whole-embryo experiments, show that Wnt signalling regulates heart development at the level of GATA factors, confirming earlier results from tissue-culture experiments. Furthermore, our rescue experiments in Xenopus embryos revealed differences in functional activity between the various GATA transcription factors involved in heart development. We discovered that GATA4 is more efficient at reinstating the gene expression of other pro-cardiogenic transcription factors, whereas GATA6 is more potent at promoting the expression of genes associated with terminal heart muscle differentiation. In conclusion, our findings show that the inhibition of heart development by Wnt/beta-catenin signalling during organogenesis is mediated by the loss of expression of GATA pro-cardiogenic transcription factors and reveal functional differences between those GATA factors in heart development.
Afouda,
GATA transcription factors integrate Wnt signalling during heart development.
2008,
Pubmed
,
Xenbase
Afouda,
GATA4, 5 and 6 mediate TGFbeta maintenance of endodermal gene expression in Xenopus embryos.
2005,
Pubmed
,
Xenbase
Ariizumi,
Amphibian in vitro heart induction: a simple and reliable model for the study of vertebrate cardiac development.
2003,
Pubmed
,
Xenbase
Brewer,
GATA factors lie upstream of Nkx 2.5 in the transcriptional regulatory cascade that effects cardiogenesis.
2005,
Pubmed
Brewer,
The human and mouse GATA-6 genes utilize two promoters and two initiation codons.
1999,
Pubmed
Brewer,
GATA factors in vertebrate heart development and disease.
2006,
Pubmed
Chambers,
The RSRF/MEF2 protein SL1 regulates cardiac muscle-specific transcription of a myosin light-chain gene in Xenopus embryos.
1994,
Pubmed
,
Xenbase
Cohen,
Wnt signaling: an essential regulator of cardiovascular differentiation, morphogenesis and progenitor self-renewal.
2008,
Pubmed
Drysdale,
Cardiac troponin I is a heart-specific marker in the Xenopus embryo: expression during abnormal heart morphogenesis.
1994,
Pubmed
,
Xenbase
Evans,
tinman, a Drosophila homeobox gene required for heart and visceral mesoderm specification, may be represented by a family of genes in vertebrates: XNkx-2.3, a second vertebrate homologue of tinman.
1995,
Pubmed
,
Xenbase
Fu,
Vertebrate tinman homologues XNkx2-3 and XNkx2-5 are required for heart formation in a functionally redundant manner.
1998,
Pubmed
,
Xenbase
Garriock,
Census of vertebrate Wnt genes: isolation and developmental expression of Xenopus Wnt2, Wnt3, Wnt9a, Wnt9b, Wnt10a, and Wnt16.
2007,
Pubmed
,
Xenbase
Grow,
Tinman function is essential for vertebrate heart development: elimination of cardiac differentiation by dominant inhibitory mutants of the tinman-related genes, XNkx2-3 and XNkx2-5.
1998,
Pubmed
,
Xenbase
Haworth,
GATA4 and GATA5 are essential for heart and liver development in Xenopus embryos.
2008,
Pubmed
,
Xenbase
Hoppler,
Studying Wnt signaling in Xenopus.
2008,
Pubmed
,
Xenbase
Jiang,
The Xenopus GATA-4/5/6 genes are associated with cardiac specification and can regulate cardiac-specific transcription during embryogenesis.
1996,
Pubmed
,
Xenbase
Latinkic,
Transcriptional regulation of the cardiac-specific MLC2 gene during Xenopus embryonic development.
2004,
Pubmed
,
Xenbase
Lavery,
Wnt6 signaling regulates heart muscle development during organogenesis.
2008,
Pubmed
,
Xenbase
Lavery,
Analysis of gene expression in Xenopus embryos.
2008,
Pubmed
,
Xenbase
Lavery,
Gain-of-function and loss-of-function strategies in Xenopus.
2008,
Pubmed
,
Xenbase
Marvin,
Inhibition of Wnt activity induces heart formation from posterior mesoderm.
2001,
Pubmed
,
Xenbase
Meijer,
GSK-3-selective inhibitors derived from Tyrian purple indirubins.
2003,
Pubmed
,
Xenbase
Molkentin,
Direct activation of a GATA6 cardiac enhancer by Nkx2.5: evidence for a reinforcing regulatory network of Nkx2.5 and GATA transcription factors in the developing heart.
2000,
Pubmed
,
Xenbase
Pandur,
Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis.
2002,
Pubmed
,
Xenbase
Patient,
The GATA family (vertebrates and invertebrates).
2002,
Pubmed
Peterkin,
Redundancy and evolution of GATA factor requirements in development of the myocardium.
2007,
Pubmed
,
Xenbase
Peterkin,
GATA-6 maintains BMP-4 and Nkx2 expression during cardiomyocyte precursor maturation.
2003,
Pubmed
,
Xenbase
Sakai,
Selection of DNA binding sites for human transcriptional regulator GATA-6.
1998,
Pubmed
Sasai,
Regulation of neural induction by the Chd and Bmp-4 antagonistic patterning signals in Xenopus.
1995,
Pubmed
,
Xenbase
Sato,
Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor.
2004,
Pubmed
Schneider,
Wnt antagonism initiates cardiogenesis in Xenopus laevis.
2001,
Pubmed
,
Xenbase
Small,
Myocardin is sufficient and necessary for cardiac gene expression in Xenopus.
2005,
Pubmed
,
Xenbase
Sparrow,
Regulation of the tinman homologues in Xenopus embryos.
2000,
Pubmed
,
Xenbase
Tonissen,
XNkx-2.5, a Xenopus gene related to Nkx-2.5 and tinman: evidence for a conserved role in cardiac development.
1994,
Pubmed
,
Xenbase
Warkman,
Xenopus as a model system for vertebrate heart development.
2007,
Pubmed
,
Xenbase
Warkman,
Amphibian cardiac troponin I gene's organization, developmental expression, and regulatory properties are different from its mammalian homologue.
2004,
Pubmed
,
Xenbase
Yost,
The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.
1996,
Pubmed
,
Xenbase