The development of the embryonic outflow tract provides novel insights into cardiac differentiation and remodeling

The embryonic cardiac outflow tract (OFT) connects the developing ventricles with the aortic sac. In birds and mammals, OFT cardiomyocytes are generated from a secondary (anterior), heart-forming field well after the formation of the primitive heart tube. The OFT cardiomyocytes have unique properties and developmental fates as compared with the myocytes of the atrial and ventricular chambers. Many of the OFT cardiomyocytes of the avian embryo are eliminated by programmed cell death (PCD) during OFT remodeling in the transition from a single- to a dual-series circulation. Targeted PCD gain and loss-of-function studies indicate that PCD drives the shortening and rotation of the OFT required for the aorta and pulmonary artery to connect with the left and right ventricles, respectively. Defects in this process model aspects of the relatively common and often life-threatening congenital human conotruncal heart defects. Using indicators of tissue hypoxia, we suggest that OFT myocardial hypoxia may be the trigger for the PCD-dependent remodeling of the OFT. This review discusses these aspects of the formation and remodeling of the embryonic OFT in the context of the broader questions of cardiac muscle biology. (C) 2004, Elsevier Inc.