Molecular Regulation of Cushion Morphogenesis

This chapter discusses where and how the cardiac cushions form, the constituency of the cushions, progress in deciphering the molecular regulatory networks governing the functional formation of the valve leaflets, and partitioning of a four-chambered heart. Immediately following looping of the primitive heart tube, regional expansion of the extracellular matrix (cardiac jelly) separating the outer myocardial lining and the inner endothelial lining of the heart occurs to initiate endocardial cushion morphogenesis by a process called epithelial-mesenchymal transition (EMT). This process occurs initially in the atrioventricular (AV) canal region and later in the outflow tract (OFT) to produce cushion mesenchyme. In the atrioventricular canal two main masses of cushion tissue, the dorsal or inferior atrioventricular cushion and the ventral or superior atrioventricular endocardial cushion, originate from the epithelial-mesenchymal transition. There are two lateral cushions that contribute to the mural leaflets of the atrioventricular valves. The atrioventricular canal becomes divided into two distinct right and left orifices when the two main cushion masses fuse to form the atrioventricular septum intermedium and divide the common atrioventricular canal into a right-sided tricuspid orifice and left-sided, mitral orifice. These cushions successfully establish unidirectional blood flow even before they become mesenchymalized.