Molecular Development Of The Heart

Authors: Bradley B. Keller, Andy Wessels, Robert J. Schwartz, Robert Roberts, Roger R. Markwald

The wide spectrum of congential cardiovascular anomalies that present from the prenatal period into adulthood has challenged clinicians and scientists for centuries.!,2 Equally daunting historically have been the complex and varied descriptions of cardiac embryology and the pathogenesis of congenital cardiovascular malformations.3-6 Fortunately, scientific advances, including the availability of cell-specific immunohistochemistry, rapid advances in molecular biological techniques, expansion of investigations into integrated embryonic cardiovascular physiology, and dramatic improvements in the three-dimensional imaging of the embryonic cardiovascular anatomy, make the specific determination of pathogenesis for most cardiovascular anomalies a realistic goal in the next decade Fig. 9-1) .E!

This chapter will discuss current ideas about normal development of the heart and vasculature and illustrate how this knowledge can help one understand the pathogenesis of congenital cardiovascular malformations. As with all complex developmental events, cardiovascular morphogenesis must be defined in a stepwise fashion, and this chapter details some of these pivotal developmental events. Although many of the mechanisms that lead to the development of the fully septated, four-chambered vertebrate heart are interdependent (e.g., the formation of the muscular ventricular septum and the membranous portion of the atrioventricular septum), many of these events are discussed in separate sections for clarity. It needs to be emphasized, however, that none of these remodeling events are isolated processes (e.g., formation of the outflow tract and closure of the interventricular foramen). The information presented in this chapter focuses on human development. However, a rapidly growing number of animal models generated by using sophisticated molecular biological techniques are becoming available and will accelerate the investigation of a wide variety of aspects related to normal and aberrant cardiovascular morphogenesis.

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