Getting to the heart of cardiac morphogenesis.

Abstract

One of the most difficult concepts in heart development is to convert a looped tube with the presumptive right and left chambers in series to a 4-chambered heart with blood flowing from right atrium to right ventricle and left atrium to left ventricle. Try to explain how it happens to a room full of typical first-year medical students (“just tell me what I need to know”) if you are into self-laceration. The key to shifting from serially connected presumptive chambers to chambers connected in parallel is the atrioventricular (AV) canal. Because this little canal originally connects only the part of the tube that will become the atria with the part that becomes the left ventricle, it is critical that it moves or expands to gain access to the more distal part of the tube that will become the right ventricle. It is only possible because the tube is looped. It may be obvious that the myocardium at the inner part of the loop must be remodeled along with a change in position or expansion of the AV canal. My awakening to the complexity of this region occurred several years ago with the publication of a study by Webb et al1 in Circulation Research . Until then, my rather naive view of the AV canal was fairly simplistic and involved some shifting and fusion of the AV cushions. Webb et al presented a coherent exposition of the central mesenchymal mass (septum intermedium) in developing mouse embryos. This central mass comprises the AV endocardial cushions, the valves of the sinus venosus and the sinus septum, and mesenchyme of the right pulmonary ridge. This ridge is additionally complicated because it has a core (called the spina vestibuli) originating from body mesenchyme, which is covered by mesenchyme that is continuous with the leading …