The Epicardial Signaling Center in Development and Disease

This chapter discusses the epicardial signaling center in development and disease. The processes that occur during midgestational heart development include formation of the epicardium, myocardial growth, coronary vascular development, endocardial cushion formation, ventricular septation, and trabeculation. Other processes that occur in the midgestational heart include development of the atrial-ventricular and outflow tract endocardial cushions. These structures will give rise to the atrioventricular valves (tricuspid and mitral) and outflow tract valves (pulmonary and aortic), respectively. Proper endocardial cushion development is essential for septation of both the atrial and ventricular chambers, as defects in this important process can lead to atrial and ventricular septal defects (ASD and VSD) both in animal models and in several human genetic syndromes. Ventricular septation is further aided by the growth of the muscular interventricular septum, a process that occurs between E14.5 and E16.5 in the mouse. Lastly, trabeculation of the ventricular chambers occurs throughout midgestational heart development. This process patterns the myocardial wall into an outer compact layer and an inner trabecular layer. Little is known about the signals that regulate the formation of these finger-like extensions of myocardial tissue (trabeculae) that project into both the right and left ventricular chambers. An entity termed isolated ventricular noncompaction, which in many individuals leads to fulminant heart failure, results from the overproduction of these finger-like projections at the expense of compact myocardial tissue.