A 2-step model of vascular tube morphogenesis and sprouting: VEGF and FGF prime ECs to respond to hematopoietic stem cell cytokines to form tubes and sprout in 3D matrices. (A) A schematic is shown depicting the 2-step process of EC priming followed by tube morphogenesis and associated downstream effects connected to each step, including up-regulation of the hematopoietic cytokine receptors after VEGF-A/FGF-2 priming events, hematopoietic cytokine-induced morphogenesis, and vessel stabilization through the recruitment of pericytes and basement membrane matrix deposition. A Venn diagram compartmentalizes each growth factor on the basis of its primary function as either a priming or promorphogenic molecule. FGF-2 has strong EC priming activity but does facilitate the action of promorphogenic hematopoietic cytokines. VEGF has strong EC priming activity and also facilitates promorphogenic hematopoietic cytokines during EC sprouting events. (B) Images of VEGF/FGF-primed EC cultures stimulated with VEGF-A versus the hematopoietic factors as morphogenic cues (top). Bar equals 20 μm. VEGF/FGF primed vitelline vessel explants stimulated with VEGF-A versus the hematopoietic factors as morphogenic cues (bottom). Bar equals 100 μm.