Wnt2 is a direct downstream target of GATA6 during early cardiogenesis

Alexandrovich, Alexander; Arno, Matthew; Patient, Roger; Shah, Ajay M.; Pizzey, John; Brewer, Alison C.

doi:10.1016/j.mod.2006.02.002

Cited by 38 publications

(40 citation statements)

References 63 publications

(77 reference statements)

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“…Of course, this awaits further analyses. Interestingly, Wnt2b and Wnt11 are both direct target genes of GATA6, 49,71 and both are coexpressed in early mouse 72,73 but not in Xenopus embryos. 74,75 This putative functional redundancy might explain why a loss of Wnt11 results in an early cardiac phenotype in Xenopus 49,51 but not in the mouse with later phenotypes.…”

Section: Cardiac Specification: Positive Influence Of Noncanonical Wnmentioning

confidence: 99%

The Multiple Phases and Faces of Wnt Signaling During Cardiac Differentiation and Development

Gessert

Kühl

2010

Circulation Research

354

310

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Understanding heart development on a molecular level is a prerequisite for uncovering the causes of congenital heart diseases. Therapeutic approaches that try to enhance cardiac regeneration or that involve the differentiation of resident cardiac progenitor cells or patient-specific induced pluripotent stem cells will also benefit tremendously from this knowledge. Wnt proteins have been shown to play multiple roles during cardiac differentiation and development. They are extracellular growth factors that activate different intracellular signaling branches. Here, we summarize our current understanding of how these factors affect different aspects of cardiogenesis, starting from early specification of cardiac progenitors and continuing on to later developmental steps, such as morphogenetic processes, valve formation, and establishment of the conduction system. (Circ Res. 2010;107:186-199.)

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Section: Cardiac Specification: Positive Influence Of Noncanonical Wnmentioning

confidence: 99%

The Multiple Phases and Faces of Wnt Signaling During Cardiac Differentiation and Development

Gessert

Kühl

2010

Circulation Research

354

310

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“…2B). In cotransfection luciferase assays driven by the GATA6-dependent cardiac promoters, NPPA (25) and WNT2 (26), both GATA6-E486del and GATA6-N466H proteins were Zf, zinc finger; NLS, nuclear localization signal; CHD, congenital heart disease; PTA, persistent truncus arteriosus; ASD, atrial septal defect; PS, pulmonary stenosis; PDA, patent ductus arteriosus.…”

Section: Gata6 Mutations Cause Defects In Nuclear Localization and Thementioning

confidence: 99%

GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling

Kodo

Nishizawa

Furutani

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

214

157

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Congenital heart diseases (CHD) occur in nearly 1% of all live births and are the major cause of infant mortality and morbidity. Although an improved understanding of the genetic causes of CHD would provide insight into the underlying pathobiology, the genetic etiology of most CHD remains unknown. Here we show that mutations in the gene encoding the transcription factor GATA6 cause CHD characteristic of a severe form of cardiac outflow tract (OFT) defect, namely persistent truncus arteriosus (PTA). Two different GATA6 mutations were identified by systematic genetic analysis using DNA from patients with PTA. Genes encoding the neurovascular guiding molecule semaphorin 3C (SEMA3C) and its receptor plexin A2 (PLXNA2) appear to be regulated directly by GATA6, and both GATA6 mutant proteins failed to transactivate these genes. Transgenic analysis further suggests that, in the developing heart, the expression of SEMA3C in the OFT/subpulmonary myocardium and PLXNA2 in the cardiac neural crest contributing to the OFT is dependent on GATA transcription factors. Together, our data implicate mutations in GATA6 as genetic causes of CHD involving OFT development, as a result of the disruption of the direct regulation of semaphorin-plexin signaling.congenital heart disease ͉ persistent truncus arteriosus ͉ cardiac neural crest C ongenital heart diseases (CHD) constitute a major percentage of clinically significant birth defects with an estimated prevalence of 4-10 per 1,000 live infants (1). Cardiac outflow tract (OFT) defects are estimated to account for approximately 30% of CHD (2) and usually require an intervention during the first year of life. A variety of OFT defects results from disturbance of the morphogenetic patterning of the anterior pole of the heart, which is essential for the establishment of separate systemic and pulmonary circulations in higher vertebrates. Persistent truncus arteriosus (PTA), which is attributed to missing septation of the OFT, is recognized as the most severe phenotype of OFT defect, and is often associated with an unfavorable prognosis because complete surgical repair is not always possible (3). Although an improved understanding of possible genetic causes would provide insight into the pathogenesis of CHD and allow for better assessment of disease risk, prenatal diagnosis, and critical information for disease prevention, the etiology of most CHD, including OFT defects, remains unknown because of the multifactorial nature of the diseases (4-6).Based on animal studies, it appears that abnormal development of cardiac neural crest (CNC) cells, an ectoderm-derived cell lineage, contributes significantly to the pathology of OFT defects (7-12). During early embryogenesis, CNC cells arise from the dorsal neural tube and migrate ventrally as mesenchymal cells to populate the OFT, where they coalesce to form the aorticopulmonary septum, which divides the single truncus arteriosus (embryonic OFT) into the aorta and pulmonary artery, resulting in the establishment of separate systemic and pulmonary c...

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“…Wnt genes are among the non-cellautonomous targets of GATA factors (Alexandrovich et al, 2006;Afouda et al, 2008). The so-called canonical pathway involves b-catenin (Hoppler and Kavanagh, 2007); alternative, b-catenin-independent pathways are known as non-canonical pathways, one of which involves rho-GTPase, cdc42, and PKCd and may result in activation of Jun N-terminal Kinase (JNK) (Eisenberg and Eisenberg, 2006).…”

Section: Introductionmentioning

confidence: 99%

Different requirements for GATA factors in cardiogenesis are mediated by non‐canonical Wnt signaling

Afouda¹,

Hoppler²

2011

Developmental Dynamics

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GATA factors and Wnt signals are key regulators of vertebrate cardiogenesis, but specific roles for individual GATA factors and how they interact with Wnt signaling remain unknown. We use loss of function and overexpression approaches to elucidate how these molecules regulate early cardiogenesis in Xenopus. In order to minimize indirect effects due to abnormal early embryogenesis, we use pluripotent embryonic tissues as cardiogenic assays. We confirm central roles for GATA4, 5, and 6 in cardiogenesis, but also discover individual and different requirements. We show that GATA4 or 6 regulate both cardiogenic potential and subsequent cardiomyocyte differentiation but that GATA5 is involved in regulating cardiomyocyte differentiation. We also show that Wnt11b signaling can rescue reduced cardiac differentiation resulting from loss of function of GATA4 and 6 but not GATA5. We conclude that Wnt11b mediates the differential requirements for GATA factors during vertebrate cardiogenesis. Developmental Dynamics 240:649-662,

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Wnt2 is a direct downstream target of GATA6 during early cardiogenesis

Cited by 38 publications

References 63 publications

The Multiple Phases and Faces of Wnt Signaling During Cardiac Differentiation and Development

The Multiple Phases and Faces of Wnt Signaling During Cardiac Differentiation and Development

GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling

Different requirements for GATA factors in cardiogenesis are mediated by non‐canonical Wnt signaling

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