Rosa26-CreERT2 mice were purchased from the Jackson Laboratory (Stock No. 008463). VEGFR3 (Flt4) floxed mice47 (link), Vegfc floxed mice47 (link), Cdh5(PAC)-CreERT2 mice29 (link), membrane-retained VE-cadherin (Cdh5α) mice48 (link) and VE-cadherin (Cdh5) floxed49 (link) were previously described. Mice were bred according to standard protocols and maintained on a C57BL/6 or mixed background. Mating pairs were set up in the afternoon and vaginal plugs checked in the morning. For E18.5 embryo collection, tamoxifen (200μl at 25mg/ml dissolved in corn oil) was administered by oral gavage to pregnant dams on E14.5, E15.5, and E16.5 and medroxyprogesterone (100μl at 15mg/ml dissolved in DMSO) was administered by subcutaneous injection on E17.5 to prevent parturition. For E14.5 embryo collection, tamoxifen (200μl at 25mg/ml dissolved in corn oil) was administered by oral gavage to pregnant dams on either E9.5, E10.5, and E11.5 (embryos in Figure 2 and Supplemental Figure 1) or E10.5, E11.5, and E12.5 (embryos in Figures 4, 5, and 6 and Supplemental Figures 4 and 5). Cre-negative and/or heterozygous littermates were used as controls. All procedures were conducted using an approved animal protocol (806811) in accordance with the University of Pennsylvania Institutional Animal Care and Use Committee.