The cardiovascular system develops 15–16 days in gestation.
In the extraembryonic yolk sac, mesodermal precursor cells aggregate to form blood islands, the sites of development of endothelial and primitive blood cells.
Within the blood islands, centrally-located cells become primitive blood cells, whereas outer cells give rise to endothelial cells (ECs).
ECs then form the vascular primary plexus which is subsequently remodeled to form the yolk sac vasculature.
In the embryo proper, mesodermal precursor cells differentiate into the vascular primary plexus and major vessels, aorta, and cardinal vein.
The heart and blood vessels are created from the mesoderm that forms blood islands (isolated cell masses) around which the endothelial tubes are formed.
Vascular smooth muscle cells and connective tissue derived from the local mesoderm then surround the endothelial tubes.
After arterial and venous ECs are specified, the complex blood vasculature is formed via extensive remodeling. At embryonic day (E) 9.5, a subset of ECs of the cardinal vein acquires a lymphatic endothelial cell (LEC) fate and develops into lymphatic vessels.1
The heart begins to beat and blood begins to circulate throughout the blood vessel network around the 4th week of gestation.
Developmental defects include heart defects in chamber partitioning and abnormal great vessel partitioning and may be associated with maternal use of drugs, alcohol, cigarettes, retinoic acid, or exposure to rubella virus infection.