Apoptosis and epicardial contributions act as complementary factors in remodeling of the atrioventricular canal myocardium and atrioventricular conduction patterns in the embryonic chick heart

Steijn, Rebecca Vicente; Sedmera, David; Blom, Nico A.; Jongbloed, Monique R.M.; Kvasilová, Alena; Naňka, Ondřej

doi:10.1002/dvdy.24642

Cited by 7 publications

(9 citation statements)

References 38 publications

(62 reference statements)

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“…); sculpting of the conduction system and isolation of auricles from ventricles (Vicente‐Steijn et al. ); excavation of the cusps of the semilunar valve primordia (Hurle et al. ); formation of the coronary artery orifices in the aortic wall (Velkey & Bernanke, ); and control of heart size (Zhou et al.…”

Section: Discussionmentioning

confidence: 99%

Cell senescence, apoptosis and DNA damage cooperate in the remodeling processes accounting for heart morphogenesis

et al. 2019

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During embryonic development, organ morphogenesis requires major tissue rearrangements that are tightly regulated at the genetic level. A large number of studies performed in recent decades assigned a central role to programmed cell death for such morphogenetic tissue rearrangements that often sculpt the shape of embryonic organs. However, accumulating evidence indicates that far from being the only factor responsible for sculpting organ morphology, programmed cell death is accompanied by other tissue remodeling events that ensure the outcome of morphogenesis. In this regard, cell senescence has been recently associated with morphogenetic degenerative embryonic processes as an early tissue remodeling event in development of the limbs, kidney and inner ear. Here, we have explored cell senescence by monitoring β‐galactosidase activity during embryonic heart development where programmed cell death is believed to exert an important morphogenetic function. We report the occurrence of extensive cell senescence foci during heart morphogenesis. These foci overlap spatially and temporally with the areas of programmed cell death that are associated with remodeling of the outflow tract to build the roots of the great arteries and with the septation of cardiac cavities. qPCR analysis allowed us to identify a gene expression profile characteristic of the so‐called senescence secretory associated phenotype in the remodeling outflow tract of the embryonic heart. In addition, we confirmed local upregulation of numerous tumor suppressor genes including p21, p53, p63, p73 and Btg2. Interestingly, the areas of cell senescence were also accompanied by intense lysosomal activation and non‐apoptotic DNA damage revealed by γH2AX immunolabeling. Considering the importance of sustained DNA damage as a triggering factor for cell senescence and apoptosis, we propose the coordinated contribution of DNA damage, senescence and apoptotic cell death to assure tissue remodeling in the developing vertebrate heart.

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Section: Discussionmentioning

confidence: 99%

Cell senescence, apoptosis and DNA damage cooperate in the remodeling processes accounting for heart morphogenesis

et al. 2019

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“…Similarly, a lot of attention was paid to understand mechanism responsible for electrical development of mature AVJ [1,3,6] as well as formation of undesirable additional AV bypasses [7]. Although, the role of the apoptosis and fibrotic invagination in AVJ electrical maturation were recently described in our laboratory [8], the understanding of this complex process is far from complete. The inability to connect AVJ morphology with electrophysiological behavior represents main limitation in study underlining mechanisms APs resolving.…”

Section: Discussionmentioning

confidence: 99%

“…Third, since the frequency of the APs persistence in the presented work was not high enough and since the APs are often clinically connected with structural AVJ deformation, we plan additionally utilize model of epicardial inhibition [8] and model of ventricular septal defect. Both models, already established in our laboratory, could enhance underling mechanisms that can lead to APs formation in more detail.…”

Section: Discussionmentioning

confidence: 99%

“…In this case, the APs that bypass AV grove allow premature ventricular excitation and could proceed to AV re-entrant tachycardia (AVRT) [1]. Beside the fact that AVRT is a common form of supraventricular tachycardia in children and adult [2,8], the mechanisms of APs formation is poorly understood. Its prenatal origin as a remnant of initially myocardial AVJ is generally accepted [3].…”

Section: Introductionmentioning

confidence: 99%

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Optical Mapping Could Reveal Two-Dimensional Morphology of Atrioventricular Electrical Insulation in the Foetal Avian Heart

Olejníčková

Janoušek

Ronzhina

et al. 2018

2018 Computing in Cardiology Conference (CinC)

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Syndromes of ventricular pre-excitation or atrioventricular (AV) re-entry are believed to results from inappropriate formation of the AV junction (AVJ) during prenatal development. However, technical limitations pose challenge to study foetal heart electrophysiology and are hampering understanding formation of accessory pathways (APs) bypassing AVJ. Here, we present a novel approach of retrograde perfusion for optical mapping of chicken foetal heart. Together with embryonic heart mapping, we were able to investigate AVJ electrical remodelling during the entire prenatal period. AV electrical insulation was observed concomitant to functional deployment of the conduction system at the time of ventricular septation. However, persistence of ectopic AV electrical continuity was still detected in postseptation foetal hearts. APs registered in 40% of prenatal day 13 (localised in the central anterior or left posterior side) were progressively resolved and none were detected on prenatal day 18. The optical mapping approach thus proved its ability to track AVJ electrical remodelling during whole prenatal chicken development and spatiotemporally localise electrically active APs.

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“…50 Recent experiments suggest that coronary endothelial cells have a heterogeneous origin, including sinus venosus endotheliumderived cells and surface mesothelium-derived cells. 66 Additional studies in chicken embryos suggest that the epicardium may be involved in the autonomic response during early cardiac development, 68 correct atrioventricular electrical conduction patterns, 158 and appropriate differentiation of Purkinje fibers. 33 Numerous studies have investigated the contributions of the epicardium toward the cardiomyocyte pool, but so far the evidence suggests that the epicardium does not contribute (at least in avian species) to myocardial lineages.…”

Section: How Chicken Embryos Have Informed the Understanding Of Epicamentioning

confidence: 99%

Embryonic Chicken (Gallus gallus domesticus) as a Model of Cardiac Biology and Development

Vilches-Moure

2019

comp med

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Cardiovascular disease remains one of the top contributors to morbidity and mortality in the United States. Increasing evidence suggests that many processes, pathways, and programs observed during development and organogenesis are recapitulated in adults in the face of disease. Therefore, a heightened understanding of cardiac development and organogenesis will help increase our understanding of developmental defects and cardiovascular diseases in adults. Chicks have long served as a model system in which to study developmental problems. Detailed descriptions of morphogenesis, low cost, accessibility, ease of manipulation, and the optimization of genetic engineering techniques have made chicks a robust model for studying development and make it a powerful platform for cardiovascular research. This review summarizes the cardiac developmental milestones of embryonic chickens, practical considerations when working with chicken embryos, and techniques available for use in chicks (including tissue chimeras, genetic manipulations, and live imaging). In addition, this article highlights examples that accentuate the utility of the embryonic chicken as model system in which to study cardiac development, particularly epicardial development, and that underscore the importance of how studying development informs our understanding of disease.

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Apoptosis and epicardial contributions act as complementary factors in remodeling of the atrioventricular canal myocardium and atrioventricular conduction patterns in the embryonic chick heart

Cited by 7 publications

References 38 publications

Cell senescence, apoptosis and DNA damage cooperate in the remodeling processes accounting for heart morphogenesis

Cell senescence, apoptosis and DNA damage cooperate in the remodeling processes accounting for heart morphogenesis

Optical Mapping Could Reveal Two-Dimensional Morphology of Atrioventricular Electrical Insulation in the Foetal Avian Heart

Embryonic Chicken (Gallus gallus domesticus) as a Model of Cardiac Biology and Development

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