by their expression of the transcription factor Tbx18.6,7 When first seen, the pulmonary vein in both the murine and human heart drains to the heart directly adjacent to the atrioventricular junction (see Fig 3.11) There is then significant remodeling so that, at first, separate orifices drain the blood from the right and left lungs Eventually, in the human heart, four orifices are formed at the corners of the atrial root (Fig 3.12) Only at the late stages is it possible to see formation of the so-called secondary atrial septum, which is no more than the fold between the right-sided pulmonary veins and the systemic venous tributaries (see Fig 3.12) FIG 3.12 Section from a human embryo after the completion of septation at 8 weeks’ gestation The pulmonary venous component now forms the left atrial roof Note the diminution in size of the left superior caval vein, and appearance of the superior interatrial fold (arrow) It is the fold that provides a superior buttress for the flap valve of the oval foramen The vestibular spine and mesenchymal cap have muscularized to form the inferior buttress of the atrial septum Septation of the Atrial Chambers The shift rightward of the tributaries of the systemic venous sinus, so that they open exclusively to the developing right atrium, permits septation of the atrial component of the heart By this stage, the addition of the new mediastinal myocardium has formed the larger part of the body of the developing atrial component (see Fig 3.7) The atrioventricular canal, of course, was present from the outset, and is also composed of primary myocardium The myocardium of the atrial component itself was also initially composed of primary myocardium, but as we have seen, the two appendages balloon in symmetrical fashion from this lumen tract (see Fig 3.6) It is at this stage that the primary atrial septum, or “septum primum,” grows as a shelf from the atrial roof (Fig 3.13) By the time the primary atrial septum has appeared, endocardial cushions have also developed within the atrioventricular canal The cushions, positioned superiorly and inferiorly within the canal, grow toward each other to divide it into rightsided and left-sided channels As the cushions grow toward each other, so the primary septum also grows toward the cushions, carrying on its leading edge a further collection of endocardial tissue, the mesenchymal cap By the time the primary septum and mesenchymal cap have approached the cushions, the cranial part of the septum, at its origin from the atrial roof, has broken down, creating the secondary interatrial foramen The primary foramen is the diminishing space between the mesenchymal cap and the fusing atrioventricular endocardial cushions (Fig 3.14) Fusion of the mesenchymal cap with the endocardial cushions obliterates the primary atrial foramen Since this process occurs to the right side of the pulmonary ridges, the solitary opening of the newly canalized pulmonary vein is committed to the left side of the dividing atrial component The base of the newly formed atrial septum, formed by the mesenchymal cap, is then further reinforced by growth into the heart of mesenchymal tissues through the right pulmonary ridge Initially illustrated by Wilhelm His the Elder, this protrusion seen in the caudal wall of the atrium was labeled the vestibular spine, or “spina vestibuli” (Fig 3.15).8 It is now frequently described as the dorsal mesenchymal protrusion FIG 3.13 Frontal section from a developing human embryo at Carnegie stage 14 The primary atrial septum can be seen growing from the atrial roof, carrying on its leading edge a cap of mesenchyme At this early stage, the atrioventricular canal, which has significant length, opens exclusively into the developing left ventricle (LV) RV, Right ventricle