During the time of cardiac looping, at approximately 3 weeks of development, the arterial and venous poles of the heart decrease or cease cell division. At the same time, cardiomyocytes at two distinct locations within the intervening tissue reinitiate cell proliferation. This localized expansion of cardiomyocytes gives rise anteriorly to the atria and posteriorly to the left ventricle, with the area separating the two regions giving rise to the atrioventricular canal. Studies in chickens and mice demonstrated that the atria grow not only through proliferation but also by the recruitment of cells to the venous pole of the heart. The left ventricle and the atria are largely derived from a common pool of progenitors termed the first heart field (Fig. 1.4). In contrast, the second heart field gives rise to the dorsal mesenchymal protrusion and primary atrial septum, which are tissues that are critically important for atrioventricular septation, the outflow tract, and the right ventricle. A con- served role for the second heart field is supported by the observations that abnormalities that affect the expansion of the second heart field are associated with congenital heart disease in mouse models and humans, including atrial and atrioventricular defects, as well as outflow tract abnormalities.
|FIG 1.4 Summary of heart tube derivatives.|
Contribution of cells from the second heart field to the heart is complete by the fifth week of human development. At this stage, chamber identity can be established by inspecting anatomic features and/or by the expression of left or right ventricular chamber-specific genes. As the cardiovascular system develops to support postnatal systemic and pulmonary circulations, the heart goes through a series of complex remodeling events. Critical steps in this process are the formation of the septa between individual components of the heart, with the purpose of separating the respective blood flows within the heart, and the formation of valves facilitating unidirectional flow among the respective components. Together, these two events are commonly referred to as valvuloseptal morphogenesis.