Atrial septation is initiated when the second heart field derived dorsal mesenchymal protrusion and the myocardial primary atrial septum (or septum primum) extend ventrally into the, yet undivided, common atrium. In the mouse, this process takes place between embryonic day (ED) 9.5 to 10.5; in humans the process occurs around day 30. The space between the leading edge of the atrial septum and the fusing atrioventricular cushions in the atrioventricular canal is the primary atrial foramen. As the primary atrial septum grows toward the mesenchymal atrioventricular cushions, thereby closing the primary interatrial foramen, perforations appear in the upper part of the primary atrial septum. These perforations will eventually coalesce and form the secondary interatrial foramen. As this part of atrial septation process nears completion, the secondary atrial septum (or septum secundum) appears in the space between the primary atrial septum and the left venous valve in the roof of the right atrium. Eventually, the upper part of the primary atrial septum will fuse with the secondary atrial septum, thereby closing off the secondary atrial foramen and completing the atrial septation process. Failure of fusion of the two atrial septa will lead to the congenital defect patent foramen ovale.
|FIG 1.5 Nervous tissue of embryo at 24 days and 4 weeks.|
Compared with atrial septation, the creation of the ventricular septum is a rather straightforward process. As the tubular heart expands, undergoes looping, and remodels, distinctive left and right ventricular components appear. During this process, a myocardial ridge, the interventricular septum, emerges between the left and right ventricle. Subsequent outward expansion of the ventricles, a process sometimes referred to as “ballooning,” in combination with upward growth of the interventricular septum and eventual fusion of crest of the septum with the atrioventricular cushions, completes the process of ventricular septation. Cell lineage tracing experiments in the mouse demonstrated that, like the right ventricle, the interventricular septum is largely derived from the second heart field.
The third septal structure that is required for separating the respective blood flows in the heart is found in the outflow tract. After completion of cardiac looping, a single outflow tract can be found connected to the right ventricular component of the yet unseptated heart. Septation of this outflow tract is required for the formation of an aorta, which eventually connects to the left ventricle, and a pulmonary trunk that comes from the right ventricle. Two sets of endocardial ridges are located within the outflow tract, and as a result of their fusion, these will separate the common outflow tract into an aorta and a pulmonary trunk. Failure of fusion can lead to congenital defects, including a double outlet right ventricle. The cardiac neural crest is also important in the septation process that separates aorta and pulmonary trunk. Abnormal development of the cardiac neural crest specifically affects the formation of the aorticopulmonary septum downstream of the semilunar valves (Fig. 1.5). This can result in the congenital defect common arterial trunk (or truncus arteriosus) or in aorticopulmonary window.