Cardiac morphogenesis: Specification of the four-chambered heart

Early heart morphogenesis involves a process in which embryonic precursor cells are instructed to form a cyclic contracting muscle tube connected to blood vessels, pumping fluid. Subsequently, the heart becomes structurally complex and its size increases several orders of magnitude to functionally keep up with the demands of the growing organism. Programmed transcriptional regulatory networks control the early steps of cardiac development. However, already during the early stages of its assembly, the heart tube starts to produce electrochemical potentials, contractions, and flow, which are transduced into signals that feed back into the process of morphogenesis itself. Heart morphogenesis, thus, involves the interplay between progressively changing genetic networks, function, and shape. Morphogenesis is evolutionarily conserved, but species-specific differences occur and in mouse, for instance, distinct phases of development become overlapping and compounded in an extremely fast gestation. Here, we review the early morphogenesis of the chambered heart that maintains a circulation supporting development of an organism rapidly growing in size and requirements.