The developmental anatomy of the ventricular outlets and intrapericardial arterial trunks is a source of considerable confusion. First, major problems exist because of the multiple names and definitions used to describe this region of the heart as it develops. Second, there is no agreement on the boundaries of the described components, nor on the number of ridges or cushions to be found dividing the outflow tract, and the pattern of their fusion.Evidence is also lacking concerning the role of the fused cushions relative to that of the so-called aortopulmonary septum in separating the intrapericardial components of the great arterial trunks. In this review, we discuss the existing problems, as we see them, in the context of developmental and postnatal morphology. We concentrate, in particular, on the changes in the nature of the wall of the outflow tract, which is initially myocardial throughout its length. Key features that, thus far, do not seem to have received appropriate attention are the origin, and mode of separation, of the intrapericardial portions of the arterial trunks, and the formation of the walls of the aortic and pulmonary valvar sinuses. Also as yet undetermined is the formation of the free-standing muscular subpulmonary infundibulum, the mechanism of its separation from the aortic valvar sinuses, and its differentiation, if any, from the muscular ventricular outlet septum.

There is no agreement, in the chick, about the number of the endocardial cushions within the outflow tract or their pattern of fusion. Also, little is known of their relative contributions to the formation of the arterial valves, the subpulmonary infundibulum, and the arterial valvar sinuses. As the chick heart is an important model for studying septation of the outflow tract, our objective was to clarify these issues. Normal septation of the outflow tract was studied in a series of 60 staged chick hearts, by using stained whole-mount preparations, serial sections, and scanning electron microscopy. A further six hearts were examined subsequent to hatching. At stage 21, two pairs of endocardial cushions were seen within the developing outflow tract. One pair was positioned proximally, with the other pair located distally. By stage 25, a third distal cushion had developed. This finding was before the appearance of two further, intercalated, endocardial cushions, also distally positioned, which were first seen at stage 29. In the arterial segment, the aortic and pulmonary channels were separated by the structure known as the aortopulmonary septum. The dorsal limb of this septum penetrated the distal dorsal cushion, whereas the ventral limb grew between the remaining two distal cushions, both of which were positioned ventrally. The three distal endocardial cushions, and the two intercalated endocardial cushions, contributed to the formation of the leaflets and sinuses of the arterial roots. The two proximal cushions gave rise to a transient septum, which later became transformed into the muscular component of the subpulmonary infundibulum. Concomitant with these changes, an extracardiac tissue plane was formed which separated this newly formed structure from the sinuses of the aortic root. Our study confirms that three endocardial cushions are positioned distally, and two proximally, within the developing outflow tract of the chick. Key words: heart; chick; developmental biology; scanning electron microscopy; embryology; morphogenesisThere have been numerous descriptions concerning septation of the outflow tract of the heart in different vertebrate species. It remains difficult to correlate the findings between different species, and reports regarding septation within the same species are frequently conflicting. To an extent, these difficulties reflect the formidable task of interpreting three-dimensional relationships in a structure as complex as the developing heart, but some do represent real morphologic differences between species. A firm understanding of these differences remains important, both because of the clinical significance of cardiac malformations (Anderson and Becker, 1992), and the use of animal models to establish the mechanisms of normal and abnormal development. Regardless of the species being studied, there is also considerable confusion regarding the nomenclature of the segments within the outflow tract, and their corresponding cushions.The outflow tract of the heart connects the develop...

BMP-2 and BMP-4 are known to be involved in the early events which specify the cardiac lineage. Their later patterns of expression in the developing mouse and chick heart, in the myocardium overlying the atrioventricular canal (AV) and outflow tract (OFT) cushions, also suggest that they may play a role in valvoseptal development. In this study, we have used a recombinant retrovirus expressing noggin to inhibit the function of BMP-2/4 in the developing chick heart. This procedure resulted in abnormal development of the OFT and the ventricular septum. A spectrum of abnormalities was seen ranging from common arterial trunk to double outlet right ventricle. In hearts infected with noggin virus, where the neural crest cells have been labelled, the results show that BMP-2/4 function is required for the migration of neural crest cells into the developing OFT to form the aortopulmonary septum. Prior to septation, misexpression of noggin also leads to a decrease in the number of proliferating mesenchymal cells within the proximal cushions of the outflow tract. These results suggest that BMP-2/4 function may mediate several key events during cardiac development.