Cardiac Septation: A Late Contribution of the Embryonic Primary Myocardium to Heart Morphogenesis

Heart morphogenesis comprises 2 major consecutive steps, viz. chamber formation followed by septation. Septation is the remodeling of the heart from a single-channel peristaltic pump to a dual-channel, synchronously contracting device with 1-way valves. In the human heart, septation occurs between 4 and 7 weeks of development. Cardiac looping and chamber formation bring the contributing structures into position to engage in septation. Cardiomyocytes that participate in chamber formation do not materially contribute to septation. The (re)discovery of the role of extracardiac mesenchymal tissue in atrioventricular septation, the appreciation that the formation of the right atrioventricular connection is more than a mere rightward expansion of the atrioventricular canal, the awareness that myocardium originating from the so-called anterior heart field regresses after its function as outflow-tract sphincter ceases, and the recent finding that the myocardialized proximal portion of the outflow-tract septum becomes the supraventricular crest have all significantly enhanced our understanding of the morphogenetic processes that contribute to septation. The bifurcation of the ventricular conduction system is the landmark that separates the contribution of the atrioventricular cushions and the outflow-tract ridges to septation and that divides the muscular ventricular septum in inlet, trabecular, and outlet portions.