Apoptosis in the developing mouse heart

被引:38
作者
Barbosky, Laura
Lawrence, David K.
Karunamuni, Ganga
Wikenheiser, Jamie C.
Doughman, Yong-Qiu
Visconti, Richard P.
Burch, John B. E.
Watanabe, Michiko
机构
[1] Case Western Reserve Univ, Sch Med, Dept Pediat, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA
[2] Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC USA
[3] Fox Chase Canc Ctr, Dept Cell & Dev Biol, Philadelphia, PA USA
关键词
programmed cell death; cardiogenesis; conotruncus; bulbus; ventricle; hypoxia; HIF-1;
D O I
10.1002/dvdy.20885
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
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 HIF1 alpha 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. (c) 2006 Wiley-Liss, Inc.
引用
收藏
页码:2592 / 2602
页数:11
相关论文
共 64 条
[1]   Development of the heart: (3) Formation of the ventricular outflow tracts, arterial valves, and intrapericardial arterial trunks [J].
Anderson, RH ;
Webb, S ;
Brown, NA ;
Lamers, W ;
Moorman, A .
HEART, 2003, 89 (09) :1110-1118
[2]   Mechanisms of caspase activation [J].
Boatright, KM ;
Salvesen, GS .
CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (06) :725-731
[3]   DEVELOPMENT OF THE ORIGIN OF THE CORONARY-ARTERIES, A MATTER OF INGROWTH OR OUTGROWTH [J].
BOGERS, AJJC ;
GITTENBERGERDEGROOT, AC ;
POELMANN, RE ;
PEAULT, BM ;
HUYSMANS, HA .
ANATOMY AND EMBRYOLOGY, 1989, 180 (05) :437-441
[4]   GATA transcription factors and cardiac development [J].
Charron, F ;
Nemer, M .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 1999, 10 (01) :85-91
[5]   Spatiotemporal and tissue specific distribution of apoptosis in the developing chick heart [J].
Cheng, G ;
Wessels, A ;
Gourdie, RG ;
Thompson, RP .
DEVELOPMENTAL DYNAMICS, 2002, 223 (01) :119-133
[6]   An Nkx-dependent enhancer regulates cGATA-6 gene expression during early stages of heart development [J].
Davis, DL ;
Wessels, A ;
Burch, JBE .
DEVELOPMENTAL BIOLOGY, 2000, 217 (02) :310-322
[7]  
DELACRUZ MV, 1977, J ANAT, V123, P661
[8]  
DELACRUZ MV, 2001, J ANAT, V17, pS13
[9]  
Epstein J A, 2001, Trends Genet, V17, pS13, DOI 10.1016/S0168-9525(01)02450-7
[10]   Coronary artery and orifice development is associated with proper timing of epicardial outgrowth and correlated Fas ligand associated apoptosis patterns [J].
Eralp, I ;
Lie-Venema, H ;
DeRuiter, MC ;
van den Akker, NMS ;
Bogers, AJJC ;
Mentink, MMT ;
Poelmann, RE ;
Gittenberger-de Groot, AC .
CIRCULATION RESEARCH, 2005, 96 (05) :526-534