The cardiovascular system is the first functional organ system to develop in the mammalian embryo. Early during development, it consists mainly of vascular endothelial cells (ECs), which form tubes connected with the heart. Later in development, these vascular tubes develop and branch into a more complex tubular system with a variety of tissue-specific properties. Some of these vascular properties develop when ECs receive signals such as growth factors from surrounding nonvascular tissue cells.

Because blood vessels are present in theembryoat the onset of organogenesis, it is reasonable to expect that they shape the development of organ tissues. Indeed, the pancreas and liver consist of tissues whose features are shaped by signals derived from vascular ECs.

The fact that tissue cells are modulated by signals from ECs and that, in turn, EC phenotypes are influenced by tissue derived signals, suggests that the development of vascularized tissues is critically dependent on mutual signaling. This mutual signaling results in structural and functional coupling between tissues and their respective vascular beds.

THE PRINCIPLE OF MUTUAL SIGNALING

The dorsal aorta is the first intraembryonic artery to form in vertebrates. Despite some differences between vertebrate species, the aorta normally develops through migration of angioblasts from the lateral plate mesoderm towards the midline of the embryo and subsequent formation of a vascular tube connected with the heart. The venous blood vessels, such as the cardinal veins, develop at around the same time and, together with heart and aorta, form the first circulatory system within the embryo. In mammals, additional blood vessels are present, such as those needed to connect embryonic and maternal circulations.