Apoptosis in the developing mouse heart

Apoptosis occurs at high frequency in the myocardium of the developing avian cardiac outflow tract (OFT). Up‐ or down‐regulating apoptosis results in defects resembling human conotruncal heart anomalies. This finding suggested that regulated levels of apoptosis are critical for normal morphogenesis...

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Bibliographic Details
Published in:	Developmental dynamics Vol. 235; no. 9; pp. 2592 - 2602
Main Authors:	Barbosky, Laura, Lawrence, David K., Karunamuni, Ganga, Wikenheiser, Jamie C., Doughman, Yong‐Qiu, Visconti, Richard P., Burch, John B.E., Watanabe, Michiko
Format:	Journal Article
Language:	English
Published:	New York Wiley‐Liss, Inc 01-09-2006
Subjects:	Animals Apoptosis bulbus cardiogenesis Caspase 3 Caspases - metabolism Chick Embryo conotruncus Female Fetal Heart - cytology Fetal Heart - metabolism Gestational Age Heart - embryology HIF‐1 Humans hypoxia Hypoxia - metabolism In Situ Nick-End Labeling Male Mice Mice, Inbred C57BL Mice, Transgenic Pregnancy programmed cell death Species Specificity Staining and Labeling ventricle
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Summary:	Apoptosis occurs at high frequency in the myocardium of the developing avian cardiac outflow tract (OFT). Up‐ or 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 end‐labeling (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 HIF1α 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. Developmental Dynamics 235:2592–2602, 2006. © 2006 Wiley‐Liss, Inc.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1058-8388 1097-0177
DOI:	10.1002/dvdy.20885