Morphogenesis and molecular considerations on congenital cardiac septal defects

Groot, Adriana C. Gittenberger‐de; Calkoen, Emmeline E.; Poelmann, Robert E.; Bartelings, Margot M.; Jongbloed, Monique R.M.

doi:10.3109/07853890.2014.959557

Cited by 58 publications

(62 citation statements)

References 110 publications

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“…We use WT1 as marker for a subpopulation of the splanchnic mesoderm that forms such tissues as the mesothelial lining of the body wall [56], which in turn gives rise to the epicardium and pericardium. The arterial epicardium [14, 15, 57] covers the arterial roots as described here. Whether the WT1 positive mesenchyme in the arterial pole derives from the epicardial epithelium or vice versa is uncertain as WT1 is able to activate both epithelium–mesenchyme transition and mesenchyme–epithelium transition [47].…”

Section: Discussionmentioning

confidence: 99%

Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart

Poelmann

Groot

Biermans

et al. 2017

EvoDevo

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BackgroundCardiac outflow tract patterning and cell contribution are studied using an evo-devo approach to reveal insight into the development of aorto-pulmonary septation.ResultsWe studied embryonic stages of reptile hearts (lizard, turtle and crocodile) and compared these to avian and mammalian development. Immunohistochemistry allowed us to indicate where the essential cell components in the outflow tract and aortic sac were deployed, more specifically endocardial, neural crest and second heart field cells. The neural crest-derived aorto-pulmonary septum separates the pulmonary trunk from both aortae in reptiles, presenting with a left visceral and a right systemic aorta arising from the unseptated ventricle. Second heart field-derived cells function as flow dividers between both aortae and between the two pulmonary arteries. In birds, the left visceral aorta disappears early in development, while the right systemic aorta persists. This leads to a fusion of the aorto-pulmonary septum and the aortic flow divider (second heart field population) forming an avian aorto-pulmonary septal complex. In mammals, there is also a second heart field-derived aortic flow divider, albeit at a more distal site, while the aorto-pulmonary septum separates the aortic trunk from the pulmonary trunk. As in birds there is fusion with second heart field-derived cells albeit from the pulmonary flow divider as the right 6th pharyngeal arch artery disappears, resulting in a mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the main septal and parietal endocardial cushions receive neural crest cells that are functional in fusion and myocardialization of the outflow tract septum. Longer-lasting septation in crocodiles demonstrates a heterochrony in development. In other reptiles with no indication of incursion of neural crest cells, there is either no myocardialized outflow tract septum (lizard) or it is vestigial (turtle). Crocodiles are unique in bearing a central shunt, the foramen of Panizza, between the roots of both aortae. Finally, the soft-shell turtle investigated here exhibits a spongy histology of the developing carotid arteries supposedly related to regulation of blood flow during pharyngeal excretion in this species.ConclusionsThis is the first time that is shown that an interplay of second heart field-derived flow dividers with a neural crest-derived cell population is a variable but common, denominator across all species studied for vascular patterning and outflow tract septation. The observed differences in normal development of reptiles may have impact on the understanding of development of human congenital outflow tract malformations.

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Section: Discussionmentioning

confidence: 99%

Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart

Poelmann

Groot

Biermans

et al. 2017

EvoDevo

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“…Another new finding that we could not, however, link to a clear semilunar valve or OFT malformation was the extremely deep extension of the parietal cushion related to the intercalated aortic cushion. The frequent observation of a perimembranous VSD could be understood from the malalignment of outflow cushions and/or septal components (Gittenberger‐de Groot et al, ; Poelmann et al, ). The finding of only a single case of AVSD supports the conclusion that these malformations are mostly restricted to the ventricular and OFT part of the heart.…”

Section: Discussionmentioning

confidence: 99%

14‐3‐3epsilon controls multiple developmental processes in the mouse heart

Groot

Hoppenbrouwers

Miquerol

et al. 2016

Developmental Dynamics

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Background 14-3-3ε plays an important role in the maturation of the compact ventricular myocardium by modulating the cardiomyocyte cell cycle via p27kip1. However, additional cardiac defects are possible given the ubiquitous expression pattern of this protein. Results Germline deletion of 14-3-3ε led to malalignment of both the outflow tract (OFT) and atrioventricular (AV) cushions, with resulting tricuspid stenosis and atresia, mitral valve abnormalities, and perimembranous ventricular septal defects (VSDs). We confirmed myocardial non-compaction, and detected a spongy septum with muscular VSDs and blebbing of the epicardium. These defects were associated with abnormal patterning of p27kip1 expression in the subendocardial and possibly the epicardial cell populations. In addition to abnormal pharyngeal arch artery patterning, we found deep endocardial recesses and paucity of intramyocardial coronary vasculature as a result of defective coronary plexus remodeling. Conclusions The malalignment of both endocardial cushions provides a new explanation for tricuspid and mitral valve defects, while myocardial non-compaction provides the basis for the abnormal coronary vasculature patterning. These abnormalities might arise from p27kip1 dysregulation and a resulting defect in epithelial to mesenchymal transformation. These data suggest that 14-3-3ε, in addition to left ventricular non-compaction (LVNC), might be linked to different forms of congenital heart disease (CHD).

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“…Congenital heart disease (CHD) remains the most common congenital malformation, with atrial septal defects (ASD) present in 116 per 100,000 live births and ventricular septal defects (VSD) present in 307 per 100,000 live births (Gittenberger-de Groot et al, 2014). Holt Oram Syndrome (HOS) is an autosomal disorder associated with cardiac septal defects and is caused by dominant mutations in the T-box transcription factor Tbx5 (Basson et al, 1997; Basson et al, 1994; Basson et al, 1999; Cross et al, 2000; Holt and Oram, 1960; Li et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

The Cardiac TBX5 Interactome Reveals a Chromatin Remodeling Network Essential for Cardiac Septation

et al. 2016

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SUMMARY Human mutations in the cardiac transcription factor gene TBX5 cause Congenital Heart Disease (CHD), however the underlying mechanism is unknown. We report characterization of the endogenous TBX5 cardiac interactome and demonstrate that TBX5, long considered a transcriptional activator, interacts biochemically and genetically with the Nucleosome Remodeling and Deacetylase (NuRD) repressor complex. Incompatible gene programs are repressed by TBX5 in the developing heart. CHD missense mutations that disrupt the TBX5-NuRD interaction cause depression of a subset of repressed genes. Furthermore, the TBX5-NuRD interaction is required for heart development. Phylogenetic analysis showed that the TBX5-NuRD interaction domain evolved during early diversification of vertebrates, simultaneous with the evolution of cardiac septation. Collectively, this work defines a TBX5-NuRD interaction essential to cardiac development and the evolution of the mammalian heart, and when altered may contribute to human CHD.

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Morphogenesis and molecular considerations on congenital cardiac septal defects

Cited by 58 publications

References 110 publications

Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart

Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart

14‐3‐3epsilon controls multiple developmental processes in the mouse heart

The Cardiac TBX5 Interactome Reveals a Chromatin Remodeling Network Essential for Cardiac Septation

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