Early Development of the Heart and Great Vessels

Abstract

The cardiovascular system is one of the first organ systems to develop in the embryo. By day 21, three germ layers: endoderm, mesoderm, and ectoderm are formed by the gastrulation process. Cells in the mesoderm coalesce through a process called vasculogenesis to form two parallel endocardial tubes. Folding of the gut tube brings these two parallel endocardial tubes towards the midline enabling them to fuse into a single linear‐shaped heart tube. By day 18, the lateral plate mesoderm splits to form two layers – splanchnic (visceral) and somatic (parietal). The cells of the splanchnic mesoderm will develop into the myocardial cells of a Primary (PHF) and Secondary Heart field (SHF). By day 22, the heart begins to beat and lengthen by the addition of cells from the SHF to the PHF. This develops into the outflow tract ‐ aortic and pulmonary vessels, and the right ventricle. By day 28, the linear‐shaped heart tube contains regions called the sinus venosus, primitive atrium, primitive ventricle, and bulbus cordis (outflow). The proximal and distal ends become “fixed” by the pericardium, the bulbus cordis and primitive ventricle grow faster than the other regions of the heart tube, and the heart bends upon itself to form a u‐shape. The primitive atrium and sinus venosus are moved dorsally, and the heart begins septation into 4 chambers. As early as day 14, two actively growing ridges called Endocardial Cushion (of the PHF) nearly divide the single lumen into two separate cavities connected by a singular (atrioventricular) canal. Subsequently, a septum grows from the cushions toward the roof of the common atrium, and from the cushions toward the apex of the primitive ventricle. Continued addition of cushion cells to the atrioventricular canal divides a single canal into a left and right canal, as well as valves attached to the ventricular wall by muscular cords. Abnormalities of Endocardial cushion can affect structures derived from the PHF. For example, Tricuspid Atresia involves the malformation of the right Atrioventricular Canal and is associated with: (i) Atrial, and (ii) Ventricular Septal Defect; (iii) hypotrophy of the right ventricle; and (iv) hypertrophy of the left ventricle. Cells of the SHF are involved in the formation and lengthening of the outflow tract. Interestingly, this growth is regulated by neural crest cells. Insults to neural crest cell development or migration can affect structures derived from the PHF. For example, Tetralogy of Fallot involves an unequal division and laterality of the bulbus cordis associated with: (1) narrow right ventricular outflow; (2) interventricular septal defect; (3) over‐riding aorta directly above the septal defect; (4) hypertrophy of the right ventricular wall because of high pressure in the right side of the heart. Neural crest cells also contribute to craniofacial development leading to facial and cardiac abnormalities in the same individual.