Intercalated cushion cells within the cardiac outflow tract are derived from the myocardial troponin T type 2 (Tnnt2) Cre lineage

Mifflin, Joshua J.; Dupuis, Loren E.; Alcala, Nicolas E.; Russell, Lea G.; Kern, Christine B.

doi:10.1002/dvdy.24641

Cited by 37 publications

(48 citation statements)

References 38 publications

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“…In both mammals and birds, but not in crocodilians, a solution for the addition of the third cusp is found by adding an intercalated swelling . All these authors agree on the importance of the SHF but vary in their explanation for the development of bicuspidy by describing either a non‐anlage of intercalated cusps or a non‐disjunction from the main endocardial OFT cushion .…”

Section: Evo‐devo Aspects Of Congenital Malformationsmentioning

confidence: 99%

“…In both mammals and birds, but not in crocodilians, a solution for the addition of the third cusp is found by adding an intercalated swelling. 133,226,227 All these authors agree on the importance of the SHF but vary in their explanation for the development of bicuspidy by describing either a non-anlage of intercalated cusps or a non-disjunction from the main endocardial OFT cushion. 133 The difference in incidence of bicuspidy in the aortic vs the pulmonary orifice might have a hemodynamic background related to the difference in mass addition of SHF cells between the aortic and pulmonary sides (as might be inferred from Scherptong et al 89 ).…”

Section: Bicuspid Semilunar Valvesmentioning

confidence: 99%

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Development and evolution of the metazoan heart

Poelmann

Groot

2019

Developmental Dynamics

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The mechanisms of the evolution and development of the heart in metazoans are highlighted, starting with the evolutionary origin of the contractile cell, supposedly the precursor of cardiomyocytes. The last eukaryotic common ancestor is likely a combination of several cellular organisms containing their specific metabolic pathways and genetic signaling networks. During evolution, these tool kits diversified. Shared parts of these conserved tool kits act in the development and functioning of pumping hearts and open or closed circulations in such diverse species as arthropods, mollusks, and chordates. The genetic tool kits became more complex by gene duplications, addition of epigenetic modifications, influence of environmental factors, incorporation of viral genomes, cardiac changes necessitated by air‐breathing, and many others. We evaluate mechanisms involved in mollusks in the formation of three separate hearts and in arthropods in the formation of a tubular heart. A tubular heart is also present in embryonic stages of chordates, providing the septated four‐chambered heart, in birds and mammals passing through stages with first and second heart fields. The four‐chambered heart permits the formation of high‐pressure systemic and low‐pressure pulmonary circulation in birds and mammals, allowing for high metabolic rates and maintenance of body temperature. Crocodiles also have a (nearly) separated circulation, but their resting temperature conforms with the environment. We argue that endothermic ancestors lost the capacity to elevate their body temperature during evolution, resulting in ectothermic modern crocodilians. Finally, a clinically relevant paragraph reviews the occurrence of congenital cardiac malformations in humans as derailments of signaling pathways during embryonic development.

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Section: Evo‐devo Aspects Of Congenital Malformationsmentioning

confidence: 99%

Section: Bicuspid Semilunar Valvesmentioning

confidence: 99%

Development and evolution of the metazoan heart

Poelmann

Groot

2019

Developmental Dynamics

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“…Endothelial Nos3 plays an important role in aortic valve development, as shown by the presence in Nos3−/− mice of partially penetrant R-N BAVs [16] and a study has presented a significant decrease in Nos3 protein amount in BAV compared to tricuspid aortic valve (TAV) human tissues [17]. More recently, second heart field cells have been proposed to contribute to intercalated cushion formation from which the non-coronary leaflet arises [18][19][20]. These studies have indicated that the distribution of second heart field derived cells is affected in Nos3−/− and that Notch signaling plays a critical role in the formation of the intercalated cushion.…”

Section: Introductionmentioning

confidence: 99%

Krox20 Regulates Endothelial Nitric Oxide Signaling in Aortic Valve Development and Disease

Odelin

Faure

Maurel-Zaffran

et al. 2019

JCDD

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Among the aortic valve diseases, the bicuspid aortic valve (BAV) occurs when the aortic valve has two leaflets (cusps), rather than three, and represents the most common form of congenital cardiac malformation, affecting 1–2% of the population. Despite recent advances, the etiology of BAV is poorly understood. We have recently shown that Krox20 is expressed in endothelial and cardiac neural crest derivatives that normally contribute to aortic valve development and that lack of Krox20 in these cells leads to aortic valve defects including partially penetrant BAV formation. Dysregulated expression of endothelial nitric oxide synthase (Nos3) is associated with BAV. To investigate the relationship between Krox20 and Nos3 during aortic valve development, we performed inter-genetic cross. While single heterozygous mice had normal valve formation, the compound Krox20+/−;Nos3+/− mice had BAV malformations displaying an in vivo genetic interaction between these genes for normal valve morphogenesis. Moreover, in vivo and in vitro experiments demonstrate that Krox20 directly binds to Nos3 proximal promoter to activate its expression. Our data suggests that Krox20 is a regulator of nitric oxide in endothelial-derived cells in the development of the aortic valve and concludes on the interaction of Krox20 and Nos3 in BAV formation.

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“…Finally, the non-facing aortic leaflet and pulmonary leaflet are considered to be derived from separately developing intercalated cushions on the posterior and anterior sides of the OFT, respectively ( Kramer, 1942 ; Lin et al, 2012 ). Although the development of the septal and parietal cushion has been studied intensively, the role of these intercalated cushions during development remains a challenging concept despite recent progress ( Anderson et al, 2003 ; Lin et al, 2012 ; Eley et al, 2018 ; Mifflin et al, 2018 ). For clarity of description of the valve leaflets and the correlation with the terminology used for the aortic leaflets in human patients with BAV, we will refer to the aortic leaflets as right coronary (RC), left coronary (LC) and non-coronary (NC) leaflets ( Sievers and Schmidtke, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

“…It is well established that the aorta and aortic valve are developmentally related. Neural crest ( Waldo et al, 1998 ; Jiang et al, 2000 ), endothelial ( Eisenberg and Markwald, 1995 ; Kisanuki et al, 2001 ), epicardial cell lineages ( Gittenberger-de Groot et al, 2012 ) and second heart field (SHF) ( Zaffran and Kelly, 2012 )-derived cells contribute to both the ascending aorta, the aortic valve ( Eley et al, 2018 ; Mifflin et al, 2018 ) and the various components of the aortic root (valvular leaflets, annulus, sinuses of Valsalva) ( de la Cruz et al, 1977 ; Kirby et al, 1983 ; Waldo et al, 2001 ). Mouse models of BAVs show cushion formation to be an essential process during valve formation, and defects in the contributing cell lineages are known to result in BAVs ( Biben et al, 2000 ; Lee et al, 2000 ; Macatee, 2003 ; Laforest and Nemer, 2011 ; Makki and Capecchi, 2012 ; Thomas et al, 2012 ; Mommersteeg et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Bicuspid aortic valve formation: Nos3 mutation leads to abnormal lineage patterning of neural crest cells and the second heart field

Peterson

Chughtai

Wisse

et al. 2018

Disease Models &Amp; Mechanisms

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The bicuspid aortic valve (BAV), a valve with two instead of three aortic leaflets, belongs to the most prevalent congenital heart diseases in the world, occurring in 0.5-2% of the general population. We aimed to understand how changes in early cellular contributions result in BAV formation and impact cardiovascular outflow tract development. Detailed 3D reconstructions, immunohistochemistry and morphometrics determined that, during valvulogenesis, the non-coronary leaflet separates from the parietal outflow tract cushion instead of originating from an intercalated cushion. Nos3−/− mice develop a BAV without a raphe as a result of incomplete separation of the parietal outflow tract cushion into the right and non-coronary leaflet. Genetic lineage tracing of endothelial, second heart field and neural crest cells revealed altered deposition of neural crest cells and second heart field cells within the parietal outflow tract cushion of Nos3−/− embryos. The abnormal cell lineage distributions also affected the positioning of the aortic and pulmonary valves at the orifice level. The results demonstrate that the development of the right and non-coronary leaflets are closely related. A small deviation in the distribution of neural crest and second heart field populations affects normal valve formation and results in the predominant right-non-type BAV in Nos3−/− mice.

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Intercalated cushion cells within the cardiac outflow tract are derived from the myocardial troponin T type 2 (Tnnt2) Cre lineage

Cited by 37 publications

References 38 publications

Development and evolution of the metazoan heart

Development and evolution of the metazoan heart

Krox20 Regulates Endothelial Nitric Oxide Signaling in Aortic Valve Development and Disease

Bicuspid aortic valve formation: Nos3 mutation leads to abnormal lineage patterning of neural crest cells and the second heart field

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