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Cardiac development: a morphologically integrated molecular approach

CONGENITAL CARDIOVASCULAR MALFORMATIONS are the most frequent defects seen in humans at birth, and in those dying prior to birth, with a recorded incidence of about 1% in liveborn infants, 10% in stillbirths, and an assumed incidence of 20% in spontaneous abortions. They are, in their own right, a source for basic research in cardiac development. They also reflect the complexity of cardiac morphogenesis, indicating that certain steps in the development of the four-chambered heart are particularly prone to errors. The formation of the heart requires interplay between various cell types, and involves processes such as cell division, apoptosis, differentiation, transdifferentiation, patterning and migration. Classic reports have considered the histogenesis and morphological development of the heart. The molecular mechanisms of the individual processes are now being unraveled at a rapid rate (for review, see reference). How these processes work together to form a functioning heart, transforming a single tube into a fourchambered heart, is a fascinating question. In this review, we offer a perspective on the development of the heart by integrating molecular and morphologic descriptions. The descriptions of morphology, however, deviate in several aspects from conventionally accepted accounts.