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In the first part of our review of cardiac development,1 we discussed the initial changes involved in transformation of the heart forming regions of the embryo into the great veins, the atrial and ventricular chambers, and the arterial trunks. We showed that this first part of cardiac development could be divided into phases of formation of the primary myocardial tube, looping of the tube, during which additional parts are added that give the future compartments their definitive topography, and the assembly of these components into the cardiac chambers and arterial trunks. In this second review, we discuss the processes that complete the separation of the two sides of the definitive heart, for the most part involving septation of the parts of the primary tube not themselves directly involved in formation of the chamber-specific compartments of the atriums and ventricles. In this respect, when concluding our first review, we explained how the arterial trunks were also formed by septation within the solitary outflow tract of the primary heart tube. We also showed, however, that subsequent to formation of the two arterial trunks, there was disappearance of the cushions that initially divided them. Thus, in the definitive heart, the proximal parts of the aorta and pulmonary trunk, along with the sinuses of the arterial roots and the subpulmonary infundibulum, possess their own discrete walls, separated by extra-cardiac space. Although septation by fusion of endocardial cushions will be a topic included in this second review, septation and separation of the outflow tracts is sufficiently complicated to require special treatment. Because of this, we will devote a third review specifically to the mechanisms underscoring the remodelling of the outflow tracts. In this review, therefore, we will confine our considerations to the formation of the atrial, atrioventricular, and ventricular septal structures. As will become …

Through the 20th century, knowledge of the events occurring during cardiac development was clouded by conflicting descriptions, coupled with use of notably different terminologies. Furthermore, not all accounts were based on direct study of embryonic material, instead being constructed on the basis of interpretations of previous reports, supported by inferences made from the structure of the congenitally malformed heart. Such processes, in themselves, are understandable, since it is axiomatic that proper appreciation of the events occurring during formation of the heart will aid in the analysis of the morphogenesis of cardiac malformations, this being a desirable prerequisite in the search for optimal treatment. Over the past decade, this has all changed. There has been an explosion of work, both anatomical and molecular, devoted to cardiac development. Advances in technology, coupled with the use of suitable animal models, now enable us to provide a more accurate account of the steps involved in formation and septation of the cardiac chambers. Not all of this new information is concordant with the “classical” accounts. In these reviews, therefore, we will describe, first, the steps involved in formation of the primary heart tube, and its conversion to the four cardiac chambers and the paired arterial trunks. We will then look in greater detail at the events occurring during the separation of the initial solitary heart tube into discrete systemic and pulmonary circulations. The mesodermal tissues that give rise to the heart first become evident when the embryo is undergoing the process known as gastrulation. In the human, this occurs during the third week of development, while for the mouse, at a comparable stage of development, around seven days will have elapsed from fertilisation, and the embryo will be in the presomitic stage. The embryonic plate in humans, initially possessing two layers, is ovoid, and is …