protrudes in oblique fashion into the distal part of the outflow tract, thus forming an embryonic aortopulmonary septum (Fig 3.26) During this period of ingrowth of the nonmyocardial components of the distal outflow tract, there is accompanying marked diminution in size of the right-sided arteries that run from the aortic sac to join the descending aorta As the dorsal parts of the arteries running within the right-sided pharyngeal arches begin to involute, it becomes possible to recognize the developing pulmonary arteries They take their origin from the floor of the aortic sac, extending caudally within the ventral mesenchyme of the mediastinum to feed the rapidly growing lung buds As the artery running within the right-sided sixth arch involutes, the orifice of the leftsided sixth arch artery becomes appreciably larger, extending to join the descending aorta as the arterial duct (Fig 3.27) FIG 3.26 Image taken from an episcopic dataset prepared from a developing mouse at embryonic day 11.5 showing a short-axis section through the junction between the aortic sac and the distal outflow tract The short arrows show how the distal myocardial border has regressed relative to the margins of the pericardial cavity, forming the parietal walls of the intrapericardial aorta and pulmonary trunk The ventral protrusion of the dorsal wall of the aortic sac is separating the cavity into the pulmonary and aortic channels, with the protrusion forming an embryonic aortopulmonary septum The space between the leading edge of the protrusion and the distal margin of the outflow cushions is the embryonic aortopulmonary foramen (double-headed arrow) FIG 3.27 Left-sided view of a reconstruction of the arteries coursing through the pharyngeal arches of a developing mouse at embryonic day 12.5 The distal part of the outflow tract has now separated into the intrapericardial arterial trunks, with the pulmonary trunk arising cranially and the aortic root positioned caudally The third and fourth arch arteries have now become the brachiocephalic artery on the right side, with the left fourth arch artery forming the transverse component of the aortic arch The artery of the left sixth arch is now recognizable as the arterial duct The pulmonary arteries are now seen arising from the floor of the original aortic sac Note also the presence of a collateral channel extending between the terminal components of the arteries of the fourth and sixth arches These collateral channels are found in half of all developing mouse embryos They are often confused with arteries of the fifth arch, which does not exist in the mouse (Courtesy Dr Simon Bamforth, Newcastle University.) By this stage, the fourth and sixth arch arteries, arising from the cranial component of the aortic sac, have remodeled to form the brachiocephalic artery on the right side, with the left fourth arch artery persisting as the transverse part of the extrapericardial aorta (see Fig 3.27) During the same period, the protrusion taking origin from the dorsal wall of the aortic sac has grown to direct the flow from the right side of the distal outflow tract to the arteries of the third and fourth arches, with the flow from the left side directed into the left sixth arch artery In this way, the aortic and pulmonary components of the remodeling distal outflow tract are directed into the appropriate extrapericardial channels (see Fig 3.27) With continuing growth, the protrusion then fuses with the distal ends of the cushions, which themselves have developed over the same period within the components of the outflow tract, which have retained their myocardial walls (Fig 3.28) During this period, within the intermediate and proximal parts of the outflow tract, the original cardiac jelly has proliferated by the process of epithelial-to-mesenchymal transformation to form the outflow cushions These opposing cushions spiral when traced distally to proximally (Fig 3.29) FIG 3.28 Image, in comparable orientation to that shown in Fig 3.26, from a mouse at a slightly later stage of development By this stage, the aortopulmonary septum formed by the protrusion from the wall of the aortic sac has fused with the distal outflow cushions (dashed line), with the distal outflow cushions themselves also fused The fusion has obliterated the aortopulmonary foramen, converting the distal outflow tract into the intrapericardial arterial trunks A further important change is the development of the intercalated cushions (stars) in the intermediate part of the outflow tract The cushions developing within the proximal part of the outflow tract, however, are as yet unfused