Embryology of the Heart

On approximately day 16, heart progenitor cells migrate through the primitive streak to a position cranial to the neural folds where they establish a horseshoe-shaped region in the splanchnic layer of lateral plate mesoderm called the primary heart field. As they migrate, these cells are specified by the laterality pathway to contribute to right and left sides of the heart and to form specific heart regions, including the atria, left ventricle, and part of the right ventricle. The remainder of the heart, including part of the right ventricle, conus cordis, and truncus arteriosus (the outflow tract), is derived from cells in the secondary heart field (SHF). The SHF lies in splanchnic mesoderm near the floor of the posterior part of the pharynx and is regulated by neural crest cells that migrate through pharyngeal arches in this region. Disruption of the laterality pathway results in many different types of heart defects, while disruption of the SHF results in defects of the outflow tract, including transposition of the great arteries, pulmonary stenosis, DORV, and others. Induction of the cardiogenic region is initiated by anterior endoderm underlying progenitor heart cells, and causes the cells to become myoblasts and vessels. BMPs secreted by this endoderm in combination with inhibition of WNT expression induces expression of NKX2.5 the master gene for heart development. Some cells in the PHF become endothelial cells and form a horseshoe-shaped tube, while others form myoblasts surrounding the tube. By the 22nd day of development, lateral body wall folds bring the two sides of the horseshoe toward the midline where they fuse (except for their caudal [atrial] ends) to form a single, slightly bent heart tube consisting of an inner endocardial tube and a surrounding myocardial mantle. During the fourth week, the heart undergoes cardiac looping. This process causes the heart to fold on itself and assume its normal position in the left part of the thorax with the atria posteriorly and the ventricles in a more anterior position. Failure of the heart to loop properly results in dextrocardia and the heart lies on the right side. Dextrocardia can also be induced at an earlier time when laterality is established.