the second heart field The newly added tissues are nonmyocardial (see Fig 51.2B) These nonmyocardial walls extend initially as a ring with two parietal tongues The addition of the nonmyocardial tissues distally serves to produce an effective regression of the distal myocardial border away from the margins of the pericardial cavity.1–3 Concomitant with this proximal movement of the distal myocardial border of the tube, the jelly that initially surrounded the common lumen is changed, by the process of endothelial-to-mesenchymal transformation, into paired cushions They spiral when traced toward the ventricular origin of the tube When initially formed, their distal margins are confluent with the myocardial border, which has a marked “fish mouth” appearance As development proceeds, the cushions begin to fuse in distal to proximal direction This divides the parts of the tube with myocardial walls into separate channels that eventually exit from the right and left ventricles However, at the start of fusion of the cushions, the proximal border of the tube is supported exclusively by the right ventricle (see Fig 51.2B) With continuing fusion of the cushions, there is ongoing proximal regression of the distal myocardial border This is accompanied by addition of still further nonmyocardial tissues to the distal part of the outflow tract Consequent to these changes, by Carnegie stage 15 in humans and during embryonic day 11.5 in the mouse, it becomes possible to recognize a discrete nonmyocardial distal component of the tube The component that has retained its myocardial walls can itself now be identified as having distal and proximal parts, with formation of two additional cushions, known as the intercalated cushions, in its distal part (Fig 51.3A) FIG 51.3 Images taken from episcopic datasets prepared from developing mice (A) Long-axis section coming from an embryo sacrificed at embryonic day 11.5 (B) Short-axis section from a mouse sacrificed at embryonic day 12.5 The intercalated cushions (stars) are formed in the intermediate part of the overall outflow tract However, this part is the distal component of the tract that retains its myocardial walls Panel B shows how the interdigitations of the intercalated cushions with the unfused parietal parts of the major cushions produces the primordia of the developing arterial roots At these stages, the roots have yet to separate from each other The distal part that has retained its myocardial walls now occupies the intermediate component of the overall outflow tract (see Fig 51.3A) It is the nonmyocardial distal part of the overall outflow tract that now becomes separated into the intrapericardial arterial trunks This is achieved by growth into the outflow tract of an oblique protrusion from the dorsal wall of the aortic sac The protrusion grows from between the origins of the arteries of the fourth and sixth pharyngeal arches, which will become the systemic and PAs, respectively Therefore, as it grows into the pericardial cavity, the protrusion is an embryonic AP septum Concomitant with its growth toward the distal margins of the major outflow cushions, the cushions themselves have fused to separate the intermediate part of the outflow tract into the arterial roots The space between the leading edge of the protrusion and the distal margins of the fused outflow cushions is an embryonic AP foramen (see Fig 51.3A) If development proceeds normally, the protrusion fuses with the cushions, obliterating the AP foramen, and the intrapericardial arterial trunks rapidly develop their own walls It is then no longer possible to recognize any septal tissues between them Failure to close the embryonic foramen accounts for persistence of AP windows.4 However, it is a mistake to consider the lesions as aortopulmonary septal defects Abnormal development of the distal outflow tract also provides a rational explanation for direct aortic origin of one of the PAs As the protrusion from the dorsal wall of the aortic sac grows into the cavity of the distal outflow tract, it does so in markedly oblique fashion It is frequently stated that the PAs are derived from the sixth arch arteries; this is not the case The right and left PAs develop within the pharyngeal mesenchyme, taking origin from the sixth arch arteries close to their own origin from the aortic sac (Fig 51.4) Therefore it is easy to envisage that increasing or decreasing obliquity of the protrusion could leave one or other, usually the right, PA in continuity with the systemic component of the aortic sac FIG 51.4 Images made from episcopic datasets prepared from developing mice sacrificed at embryonic day 11.5 (A) Reconstruction of the lumen of the aortic sac, which gives rise to the arteries of the third, fourth, and sixth pharyngeal pouches The pulmonary arteries take their origin from the sixth arch arteries close to the sac (B) They extend caudally within the pharyngeal mesenchyme, which is an oblique cut through the left side of the sac As explained earlier, by the time the embryonic AP foramen has closed, producing the separate intrapericardial arterial trunks, the distal ends of the major outflow cushions have themselves separated the intermediate part of the outflow tract into the putative aortic and pulmonary roots The interdigitation of the major and the newly formed intercalated cushions within this part of the