Chapter 24 - Blood Vessel Formation

Abstract

Primitive blood vessels in vertebrate embryos form by a process called vasculogenesis, during which mesodermal cells differentiate into endothelial precursor cells called angioblasts. These angioblasts then differentiate into endothelial cells (ECs) and coalesce to form the earliest vessels. The subsequent growth and remodeling of the vasculature occurs by angiogenesis, during which new blood vessels sprout from pre-existing vessels. The vascular endothelial growth factor (VEGF) signaling pathway has been shown to be important for the migration, proliferation, maintenance, and survival of ECs and is critical during both vasculogenesis and angiogenesis. In addition to its important function during embryonic development, VEGF is thought to play a major role in tumor-induced neovascularization. Angiopoietin–Tie signaling is thought to be critical for the maturation and stabilization of the nascent vascular network. One of the most fundamental steps in the differentiation of the vasculature is the specification of the arterial and venous endothelium. Recent work has highlighted the role of Notch, VEGF and Hedgehog signaling in the specification of arterial identity. Classically, differences between arteries and veins were attributed to physiological factors such as the direction and pressure of blood flow. However, recent work has shown that molecular distinctions between arterial and venous endothelium can appear before the onset of blood flow. Vertebrates possess a second, blind-ended vascular system, the lymphatic system, that is responsible for clearing and draining fluids and macromolecules that leak from blood vessels into the interstitial spaces of tissues and organs. Evidence suggests that the first lymphatic endothelial cells (LECs) emerge by transdifferentiation from primitive veins. The transcription factor Prox1 is a critical regulator of LEC specification, whereas the VEGF family members VEGF-C and VEGF-D are important for LEC migration and lymphangiogenesis. During early development, newly formed vessels follow a highly stereotypic and evolutionarily well-conserved pattern of network assembly that is reminiscent of that followed by the nervous system and axon tracts. A variety of recent studies have shown that many well-known molecular pathways used for the guidance of migrating axons play an important role in the guidance and patterning of developing blood vessels.