(A) Effect of Cdk5 siRNA on Dll4-induced expression of Notch downstream target genes Hey1, Hey2 and NRARP, Hes1, and VEGFR2 in HUVECs is shown (One-Way ANOVA, Holm-Sidak, SEM, *p ≤ 0.05). Cdk5 downregulation is shown (t-test, SEM, *p ≤ 0.001). n = 3. nt: non-targeting siRNA. (B) Effect of Cdk5 inhibition by roscovitine on Dll4-induced expression of Notch downstream target genes Hey1, Hey2 and NRARP is shown (One-Way ANOVA, Tukey, SEM, *p ≤ 0.05). n = 6. (C) Effect of Cdk5 inhibition by roscovitine on Notch reporter gene activation is shown (ANOVA on Ranks, Student-Newman-Keuls, SEM, *p ≤ 0.05). n = 3. (D) Expression of the Notch downstream target genes Hey1 and Hey2 in blood vessel endothelial cells (BECs) from E16.5 control and Cdk5fl/flTie2Cre embryos is shown (t-test, SEM, *p ≤ 0.001). Expression of Notch target genes was induced by plating of BECs onto Dll4. Cdk5 downregulation is shown (t-test, SEM, *p ≤ 0.001). n = 3. (E) Expression of the Notch downstream target genes Hey1 (t-test, SEM, *p = 0.003) and Hey2 (t-test, *p = 0.012) in tumors from control versus Cdk5fl/flVECCre mice is shown. Expression of VE-Cadherin (VEC) is shown. Hey1 and Hey2 mRNA levels were normalized to VEC to compensate for the hypervascularization. n = 4.