Dynamic patterns of apoptosis in the developing chicken heart

Schaefer, Katherine S.; Doughman, Yong Qiu; Fisher, Steven A.; Watanabe, Michiko

doi:10.1002/dvdy.10463

Cited by 48 publications

(53 citation statements)

References 40 publications

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“…To assess the relative contribution of cell death to observed phenotype, whole mount supravital staining was performed in ED7 (stage 31) isolated hearts with Lysotracker Red (Schaefer et al, 2004). We observed Black arrow points to the position of left coronary artery, the right coronary artery is missing (X) in this case.…”

Section: Cellular Mechanisms Of Abnormal Ventricular Wall Developmentmentioning

confidence: 76%

“…Stock solutions (50 mL) of 1 mM LTR (Molecular Probes, Eugene, OR) in DMSO were diluted in 20 mL of PBS (Schaefer et al, 2004). The embryos on ED 7 (HH 32 -11 normoxic and 14 hypoxic embryos) were dissected to expose the heart and incubated in the LysoTracker Red (LTR) solution for 15 min at RT while rocking and washed in PBS before fixation.…”

Section: Detection Of Apoptosis On Whole Mounts-lysotracker Red Stainingmentioning

confidence: 99%

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Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

Naňka

Krizova

Fikrle

et al. 2008

The Anatomical Record

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Oxygen availability is one of the necessary prerequisites for normal embryonic development. In our previous study we found that quail embryos incubated under hypoxic conditions (16% O 2 ) die at embryonic day (ED) 9 with signs of heart failure. By ED4 and ED6 we found thinner ventricular wall and increased capillary density. We thus hypothesized that the cause of death would lie in severe myocardial and coronary maldevelopment. ED6 and 7 hypoxic hearts had thinner ventricular wall, especially left. There was a simultaneous increase in capillary density, most pronounced in the interventricular septum. This site corresponds to an area of tissue hypoxia and ensuing increased angiogenesis, and also formation of ventricular conduction system. Hypoxia had a positive effect on normal sequence of maturation of the conduction system evaluated by optical mapping at ED7. In sections from ED9 hypoxic hearts we found, in addition to thinner ventricular walls, irregularities in development of coronary tree (missing coronary ostia, absence of one coronary artery, and irregular arterial wall). This deficiency was due to decreased myocyte proliferation rather than to increased apoptosis. By Indian ink injection through the left ventricle we found in normoxic hearts regular coronary branching pattern, while in the hypoxic ones there was often only an irregular plexus. Embryonic hypoxia thus leads to increased capillarity and trabeculation to minimize diffusion distance. In the subsequent period there is a failure in organization of vascular plexus into normal vasculature, resulting in thin compact myocardium that likely leads to heart failure and embryonic death.

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Section: Cellular Mechanisms Of Abnormal Ventricular Wall Developmentmentioning

confidence: 76%

Section: Detection Of Apoptosis On Whole Mounts-lysotracker Red Stainingmentioning

confidence: 99%

Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

Naňka

Krizova

Fikrle

et al. 2008

The Anatomical Record

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“…A mechanism of cell death, predominantly present in the subaortic myocardium resulting in a shortening of the subaortic OFT, has been proposed as the mechanism for proper formation of the ventriculo-arterial connections (Watanabe et al, 1998(Watanabe et al, , 2001Schaefer et al, 2004). Cell death is a well-known mechanism in heart development and has been described to occur at the level of the OFT Vuillemin and Pexieder, 1989).…”

Section: Discussionmentioning

confidence: 99%

Morphogenesis of outflow tract rotation during cardiac development: The pulmonary push concept

Scherptong

Jongbloed

Wisse

et al. 2012

Developmental Dynamics

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Background: Understanding of cardiac outflow tract (OFT) remodeling is essential to explain repositioning of the aorta and pulmonary orifice. In wild type embryos (E9.5-14.5), second heart field contribution (SHF) to the OFT was studied using expression patterns of Islet 1, Nkx2.5, MLC-2a, WT-1, and 3D-reconstructions. Abnormal remodeling was studied in VEGF120/120 embryos. Results: In wild type, Islet 1 and Nkx2.5 positive myocardial precursors formed an asymmetric elongated column almost exclusively at the pulmonary side of the OFT up to the pulmonary orifice. In VEGF120/120 embryos, the Nkx2.5-positive mesenchymal population was disorganized with a short extension along the pulmonary OFT. Conclusions: We postulate that normally the pulmonary trunk and orifice are pushed in a higher and more frontal position relative to the aortic orifice by asymmetric addition of SHF-myocardium. Deficient or disorganized right ventricular OFT expansion might explain cardiac malformations with abnormal position of the great arteries, such as double outlet right ventricle. Developmental Dynamics 241:1413-1422, 2012. V C 2012 Wiley Periodicals, Inc.Key words: cardiac development; outflow tract; gene expression Key findings:The addition of Nkx2.5-positive myocardial precursors from the anterior heart field occurs during normal development in an asymmetrical fashion, predominantly below the left branch of the 6th pharyngeal arch artery. The continued addition of right-sided myocardium during normal development results in movement without spiralization of the OFT in which the pulmonary trunk orifice is pushed in a rightward and anterior direction, a mechanism referred to as ''pulmonary push.'' Deficient or disorganized positioning of the Nkx2.5-positive precursors, as was observed in VEGF120/120 mutants might explain cardiac malformations with side-by-side position of the great arteries, such as double outlet right ventricle.

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“…This technique has been used in the past to detect apoptosis in chicken (Schaefer et al, 2004) and rodent embryos (Zucker et al, 1998;Price et al, 2003). External surfaces of mouse embryo hearts from stages embryonic day (E) 10.5 to E18.5 were observed.…”

Section: Ltr Stainingmentioning

confidence: 99%

“…The outflow tract myocardium is the site of high levels of apoptosis in the chicken and quail embryo during the time that it undergoes dramatic morphogenesis (Pexieder, 1972(Pexieder, , 1975Hurle and Ojeda, 1979;Watanabe et al, 1998;Cheng et al, 2002;Rothenberg et al, 2002;Schaefer et al, 2004). Perturbation of the timing and levels of apoptosis at this site causes misalignment of the great vessels with the ventricular chambers (Watanabe et al, 2001;Sallee et al, 2004;Sugishita et al, 2004a,b;reviewed in Rothenberg et al, 2003;Sugishita et al, 2004c).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in the developing mouse heart

Barbosky

Lawrence

Karunamuni

et al. 2006

Developmental Dynamics

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Apoptosis occurs at high frequency in the myocardium of the developing avian cardiac outflow tract (OFT). Upor down-regulating apoptosis results in defects resembling human conotruncal heart anomalies. This finding suggested that regulated levels of apoptosis are critical for normal morphogenesis of the four-chambered heart. Recent evidence supports an important role for hypoxia of the OFT myocardium in regulating cell death and vasculogenesis. The purpose of this study was to determine whether apoptosis in the outflow tract myocardium occurs in the mouse heart during developmental stages comparable to the avian heart and to determine whether differential hypoxia is also present at this site in the murine heart. Apoptosis was detected using a fluorescent vital dye, Lysotracker Red (LTR), in the OFT myocardium of the mouse starting at embryonic day (E) 12.5, peaking at E13.5-14.5, and declining thereafter to low or background levels by E18.5. In addition, high levels of apoptosis were detected in other cardiac regions, including the apices of the ventricles and along the interventricular sulcus. Apoptosis in the myocardium was detected by double-labeling with LTR and cardiomyocyte markers. Terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick endlabeling (TUNEL) and immunostaining for cleaved Caspase-3 were used to confirm the LTR results. At the peak of OFT apoptosis in the mouse, the OFT myocardium was relatively hypoxic, as indicated by specific and intense EF5 staining and HIF1␣ nuclear localization, and was surrounded by the developing vasculature as in the chicken embryo. These findings suggest that cardiomyocyte apoptosis is an evolutionarily conserved mechanism for normal morphogenesis of the outflow tract myocardium in avian and mammalian species.

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Dynamic patterns of apoptosis in the developing chicken heart

Cited by 48 publications

References 40 publications

Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

Morphogenesis of outflow tract rotation during cardiac development: The pulmonary push concept

Apoptosis in the developing mouse heart

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