Molecular markers of cardiac endocardial cushion development

Gitler, Aaron D.; Lü, Min; Jiang, Yue Qin; Epstein, Jonathan A.; Gruber, Peter J.

doi:10.1002/dvdy.10418

Cited by 100 publications

(90 citation statements)

References 46 publications

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“…FOG-1 expression has been documented in hematopoietic progenitors, gonadal cells, and the heart (Tsang et al, 1997;Tevosian et al, 2002;Katz et al, 2003;Gitler et al, 2003), while FOG-2 has been detected in brain, gonadal somatic cells, and cardiac tissue (Tsang et al, 1997(Tsang et al, , 1998Svensson et al, 1999;Tevosian et al, 1999;Lu et al, 1999;Anttonen et al, 2003). However, little is known about FOG-1 or FOG-2 expression in endoderm derivatives.…”

Section: Resultsmentioning

confidence: 99%

GATA‐4:FOG interactions regulate gastric epithelial development in the mouse

Jacobsen¹,

Mannisto²,

Porter-Tinge³

et al. 2005

Developmental Dynamics

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Transcription factor GATA-4 is a key participant in cytodifferentiation of the mouse hindstomach. Here we show that GATA-4 cooperates with a Friend-of-GATA (FOG) cofactor to direct gene expression in this segment of gut. Immunohistochemical staining revealed that GATA-4 and FOG-1 are co-expressed in hindstomach epithelial cells from embryonic days (E) 11.5 to 18.5. The other member of the mammalian FOG family, FOG-2, was not detected in gastric epithelium. To show that GATA-4:FOG interactions influence stomach development, we analyzed Gata4 ki/ki mice, which express a mutant GATA-4 that cannot bind FOG cofactors. Sonic Hedgehog, an endoderm-derived signaling molecule normally down-regulated in the distal stomach, was over-expressed in hindstomach epithelium of E11.5 Gata4 ki/ki mice, and there was a concomitant decrease in fibroblast growth factor-10 in adjacent mesenchyme. We conclude that functional interaction between GATA-4 and a member of the FOG family, presumably FOG-1, is required for proper epithelial-mesenchymal signaling in the developing stomach. Developmental Dynamics 234:355-362, 2005.

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Section: Resultsmentioning

confidence: 99%

GATA‐4:FOG interactions regulate gastric epithelial development in the mouse

Jacobsen¹,

Mannisto²,

Porter-Tinge³

et al. 2005

Developmental Dynamics

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“…Wnt reporter transgenic mice suggest that canonical Wnt signaling is active in AVC and OFT cushion mesenchyme during this growth phase (Gitler et al, 2003;Alfieri et al, 2010;Klaus et al, 2012;Gillers et al, 2015;Cai et al, 2013;Cambier et al, 2014). Known mitogenic roles of Wnt/β-catenin signaling in other developmental contexts (reviewed by Niehrs and Acebron, 2012) further support a role for Wnt in cushion expansion.…”

Section: Introductionmentioning

confidence: 91%

Wnt/β-catenin signaling enables developmental transitions during valvulogenesis

et al. 2016

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Heart valve development proceeds through coordinated steps by which endocardial cushions (ECs) form thin, elongated and stratified valves. Wnt signaling and its canonical effector β-catenin are proposed to contribute to endocardial-to-mesenchymal transformation (EMT) through postnatal steps of valvulogenesis. However, genetic redundancy and lethality have made it challenging to define specific roles of the canonical Wnt pathway at different stages of valve formation. We developed a transgenic mouse system that provides spatiotemporal inhibition of Wnt/β-catenin signaling by chemically inducible overexpression of Dkk1. Unexpectedly, this approach indicates canonical Wnt signaling is required for EMT in the proximal outflow tract (pOFT) but not atrioventricular canal (AVC) cushions. Furthermore, Wnt indirectly promotes pOFT EMT through its earlier activity in neighboring myocardial cells or their progenitors. Subsequently, Wnt/β-catenin signaling is activated in cushion mesenchymal cells where it supports FGF-driven expansion of ECs and then AVC valve extracellular matrix patterning. Mice lacking Axin2, a negative Wnt regulator, have larger valves, suggesting that accumulating Axin2 in maturing valves represents negative feedback that restrains tissue overgrowth rather than simply reporting Wnt activity. Disruption of these Wnt/β-catenin signaling roles that enable developmental transitions during valvulogenesis could account for common congenital valve defects.

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“…96 Analyses for molecular markers of endocardial cushion development identified active Wnt/␤-catenin signaling as one feature. 97 In zebrafish, loss of APC function, which leads to an accumulation of signaling active ␤-catenin, results in unlooped hearts and excessive endocardial cushions based on an increased proliferation and EMT of endocardial cells. In contrast, overexpression of APC or Dkk1 inhibits cardiac cushion formation.…”

Section: Septation and Cardiac Valve Formationmentioning

confidence: 99%

“…Heart valve formation Required (zebrafish, chicken) [96][97][98][99][100] Not known Development of conduction system Not known Expression but no functional data 121 The role of different aspects of the Wnt signaling network during cardiac differentiation and development are given as discussed in the text.…”

Section: Disclosuresmentioning

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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Molecular markers of cardiac endocardial cushion development

Cited by 100 publications

References 46 publications

GATA‐4:FOG interactions regulate gastric epithelial development in the mouse

GATA‐4:FOG interactions regulate gastric epithelial development in the mouse

Wnt/β-catenin signaling enables developmental transitions during valvulogenesis

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

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