Blood vessels are constructed by two processes: vasculogenesis, whereby a primitive vascular network is established during embryogenesis from multipotential mesenchymal progenitors, and angiogenesis, in which preexisting vessels (both in embryo and adult) send out capillary sprouts to produce new vessels ( 1-3). Endothelial cells are centrally involved in each process: They migrate and proliferate and then assemble into tubes with tight cell-cell connections to contain the blood. Peri-endothelial support cells are recruited to encase the endothelial tubes, providing maintenance and modulatory functions to the vessels; such cells include pericytes for small capillaries, smooth muscle cells for lareer ves-abundant endothelial cells, which migrate and ~roliferate but do not assemble into tubes and functional vessels (6). Thus, these highly homologous RTKs send distinctive signals in endothelial cells.
Tie2 knockout mice die somewhat later in embryogenesis (E9.5 to E10.5). The Tie2 null phenotype is distinct from that of the VEGF receptor knockouts and is also , + Y VEGF-Rk I W l Tie2 Tiel Null (Flkl) fl) (Tek) lethality: E8.5 E8.5 E9.5-Ei0.5 E14.541 Null No No tubes Disrupted m: endothelid orwa*. vessel gg cells krmsd struchrres fu@ons w informative. ~ndothelial cells are present in normal numbers and are assembled into tubes, but the vessels are immature, lacking branching networks and proper organiza-