The embryonic outflow tract is a simple tubular structure that connects the 
single primitive ventricle with the aortic sac and aortic arch arteries. This 
structure undergoes a complex sequence of morphogenetic processes to become the 
portion of the heart that aligns the right and left ventricles with the 
pulmonary artery and aorta. Abnormalities of the outflow tract are involved in 
many clinically significant congenital cardiac defects; however, the cellular 
and molecular processes governing the development of this important structure 
are incompletely understood. Histologic and tissue-tagging studies indicate that 
the outflow tract tissues compact and are incorporated predominantly into a 
region of the right ventricle. The hypothesis tested in the current study was 
that cell death or apoptosis in the muscular portion of the outflow tract is an 
important cellular mechanism for outflow tract shortening. The tubular outflow 
tract myocardium was specifically marked by infecting myocytes of the chicken 
embryo heart with a recombinant replication-defective adenovirus expressing 
beta-galactosidase (beta-gal) under the control of the cytomegalovirus promoter. 
Histochemical detection of the beta -gal-labeled outflow tract myocytes revealed 
that the tubular structure shortened to become a compact ring at the level of 
the pulmonic infundibulum over several days of development (stages 25-32, 
embryonic days 4-8). The appearance of apoptotic cardiomyocytes was correlated 
with OFT shortening by two histologic assays, TUNEL labeling of DNA fragments 
and AnnexinV binding. The rise and fall in the number of apoptotic myocytes 
detected by histologic analyses paralleled the change in activity levels of 
Caspase-3, a protease in the apoptotic cascade, measured in outflow tract 
homogenates. These results suggest that the elimination of myocytes by 
programmed cell death is one mechanism by which the outflow tract myocardium 
remodels to form the proper connection between the ventricular chambers and the 
appropriate arterial trunks.