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. 2007 Feb 12;104(9):3219–3224. doi: 10.1073/pnas.0611206104

Fig. 7.

Fig. 7.

VEGF induces Dll4 expression in angiogenic sprouts. (a–d) GS lectin (a and c) and X-gal staining (b and d) of P12 (a and b) and P15 (c and d) OIR retinas from Dll4+/lacZ mice. Note strong Dll4 gene reporter expression in the vein (yellow and blue dots) and angiogenic sprouts in OIR retinas at P15. (e–h) X-gal staining of retinal vasculature from P7 Dll4+/lacZ mice treated for 48 h with 300 ng of hFc (e and f) or VEGF Trap (g and h). Blocking VEGF markedly reduces Dll4 expression in the tip and stalk endothelial cells. (i) Real-time PCR analysis of Dll4 expression in the retinas treated for 24 h with hFc, VEGF Trap, or VEGF165. Dll4 expression data were normalized to GAPDH. Error bars represent standard errors. (j) Interaction between VEGF and Dll4 in angiogenic sprouting. VEGF initiates proliferation and blood vessel sprouting and guides growing vessels. At the same time VEGF induces expression of Dll4 that blocks excessive proliferation and sprouting. (Original magnifications: ×40 for e and g, ×100 for a–d, and ×200 for f and h.)