Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis

Brown, Daniel D.; Martz, Shauna N.; Binder, Olav; Goetz, Sarah C.; Price, Brenda M. J.; Smith, James C.; Conlon, Frank L.

doi:10.1242/dev.01596

Cited by 129 publications

(141 citation statements)

References 59 publications

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“…Our morphological findings are generally consistent with the consequences of Tbx20 morpholino knockdown experiments in fish and frogs, which showed small, unlooped and dysmorphic hearts with poor chamber discrimination (Brown et al, 2005;Szeto et al, 2002). While the cardiac progenitor field appeared to form normally in Tbx20 mutants, there was initially a profound delay in incorporation of progenitors into the forming primary heart tube.…”

Section: Morphology and Gene Expression In Tbx20 Mutant Heartssupporting

confidence: 87%

Section: Holt Orammentioning

confidence: 99%

“…Tbx20 downregulation in frogs leads to absent (Horb and Thomsen, 1999) or dysmorphic (Brown et al, 2005) hearts. Frog Tbx20 physically interacts with Tbx5 and cardiac defects in embryos are more frequent and severe if both proteins are concomitantly inhibited (Brown et al, 2005). Enforced expression experiments in frog embryos show that mouse Tbx20 can induce mesodermal and endodermal cell fates and their coordinated cell migration (Stennard et al, 2003).…”

Section: Holt Orammentioning

confidence: 99%

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Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation

et al. 2005

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The genetic hierarchies guiding lineage specification and morphogenesis of the mammalian embryonic heart are poorly understood. We now show by gene targeting that murine T-box transcription factor Tbx20 plays a central role in these pathways, and has important activities in both cardiac development and adult function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly abnormal heart morphogenesis. Underlying these disturbances was a severely compromised cardiac transcriptional program,defects in the molecular pre-pattern, reduced expansion of cardiac progenitors and a block to chamber differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2 across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor normally expressed in non-chamber myocardium, and in the atrioventricular canal it has been proposed to inhibit chamber-specific gene expression through competition with positive factor Tbx5. Our data demonstrate a repressive activity for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus, hierarchical,repressive interactions between Tbx20 and other T-box genes and factors underlie the primary lineage split into chamber and non-chamber myocardium in the forming heart, an early event upon which all subsequent morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and contractile function were revealed by in-vivo cardiac functional analysis of Tbx20 heterozygous mutant mice. These data suggest that mutations in human cardiac transcription factor genes, possibly including TBX20,underlie both congenital heart disease and adult cardiomyopathies.

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Section: Morphology and Gene Expression In Tbx20 Mutant Heartssupporting

confidence: 87%

Section: Holt Orammentioning

confidence: 99%

Section: Holt Orammentioning

confidence: 99%

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Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation

et al. 2005

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“…Chamber formation and gene expression are perturbed (Szeto et al, 2002). A similar cardiac phenotype was observed in Tbx20 morphant Xenopus embryos (Brown et al, 2005).…”

Section: Introductionsupporting

confidence: 75%

Tbx20is essential for cardiac chamber differentiation and repression ofTbx2

et al. 2005

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“…Sections were then briefly counterstained with Eosin. Antisense DIG-labeled probes (Genius Kit, Roche) were synthesized using template cDNA encoding Ap2 (Luo et al, 2003), Bmp4 (Jones et al, 1992), Fgf8 (Christen and Slack, 1997), FrzA (Xu et al, 1998), Frzb1 (Wang et al, 1997), Frz2 Klein, 1999), Frz3 andFrz7 (Deardorff et al, 2001), Frz9 (Wheeler and Hoopler, 1999), Id2 (Martinsen et al, 2004), Islet1 (Brade et al, 2007), Msx1 (Suzuki et al, 1997), Nkx2.5 (Cleaver et al, 1996), Pax3 (Bang et al, 1997), Shh (Ekker et al, 1995), Snail1 (Essex et al, 1993), Snail2 (Mayor et al, 1995), Sox8 (O'Donnell et al, 2006, Sox9 (Spokony et al, 2002), Sox10 (Aoki et al, 2003), Tbx5 and Tbx20 (Brown et al, 2005), Wnt1 and Wnt3a (Wolda et al, 1993), Wnt2b (Landesman andSokol, 1997), and Xl-Fli (Meyer et al, 1995).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Characterization of molecular markers to assess cardiac cushions formation in Xenopus

Lee

Saint-Jeannet

2009

Developmental Dynamics

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The valves and septa of the mature heart are derived from the cardiac cushions, which develop from discrete swellings in two regions of developing heart tube: the atrioventricular (AV) canal and the ventricular outflow tract (OFT). In higher vertebrates, three distinct lineages contribute to the heart valves and septa, the endocardium, the myocardium, and the cardiac neural crest that will populate the cardiac jelly of the OFT. Very little is known about cardiac cushions development in amphibians. Here, we describe the expression of eight genes during key stages of cardiac cushion development in Xenopus. Among these genes, the Wnt antagonist Frzb1 and the transcription factors Xl-Fli, Sox8, Sox9, and Sox10 are differentially expressed in the mesenchyme of the OFT and AV cushions. These genes can be used in combination with lineage-tracing experiments to determine the embryonic origin of the cardiac cushions mesenchyme in Xenopus. Developmental Dynamics 238:3257-3265,

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Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis

Abstract: SummaryTbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis

Cited by 129 publications

References 59 publications

Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation

Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation

Tbx20is essential for cardiac chamber differentiation and repression ofTbx2

Characterization of molecular markers to assess cardiac cushions formation in Xenopus

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