Figure 1. Development of a functional vasculature from endothelial progenitor cells.

Endothelial progenitors (angioblasts) differentiate from mesodermal cells during early vertebrate development. Once formed, angioblasts may acquire arterial (red) or venous (blue) fates and coalesce to generate the first embryonic blood vessels, the dorsal aorta and cardinal vein. In zebrafish, the coordinated sorting and segregation of arterial and venous angioblasts ensures the assembly of distinct dorsal aorta and cardinal vein vessels. Angioblasts also aggregate to form blood islands, which fuse and remodel in response to haemodynamic stimuli or inherent genetic factors to generate a primitive interlaced network of arterial and venous plexi. Following their vasculogenic assembly, angiogenic remodelling of the dorsal aorta, cardinal vein and vascular plexi creates a complex hierarchical network of arteries, arterioles, capillary beds, venules and veins. Subsequent recruitment of mural cells (pericytes and vascular smooth-muscle cells (vSMCs)) stabilizes nascent vessels and promotes vessel maturation. In addition, the sprouting of lymphatic endothelial cells from venous vessels (lymphangiogenesis) seeds the lymphatic system (indicated by a dotted arrow). Moreover, the emergence of haematopoietic stem cells from arterial ‘haemogenic’ endothelium gives rise to all myeloid and lymphoid blood cell lineages. Vessel diversity is further augmented by tissue-specific specializations that alter key properties, such as permeability, or modify endothelial cells to generate vascular networks with new molecular signatures^3,123.