Notch inhibition and VEGF cooperate to induce lymphangiogenesis in vivo. (A-F) Lymphatic vessels of mouse ears were visualized by VEGFR-3 whole-mount staining (red) 2 weeks after transduction with rAAVs encoding the indicated factors. White dots indicate branchpoints. (G-L) Higher magnifications of panels A through F. Note the increased branching and circumferential hyperplasia of lymphatic vessels in the VEGF and Dll4-Fc combination shown in panels A and G. Scale bars indicate 200 μm (A-F) and 50 μm (G-L). Quantification of the branchpoints (M), as indicated by the white dots in panels A through F, and vessel area (N) per microscopic field. A indicates VEGF; C, VEGF-C, and HSA, human serum albumin. Shown are means ± SEM summarized from 2 independent experiments with n = 4-6 per group per experiment; *P < .05; **P < .01; ***P < .001.