Notably, our discovery that Ang2 and Tie1 were required for cell-surface VEGFR3 expression in the cutaneous lymphatic capillaries is consistent with previous findings that loss-of-function mutations of Ang2, and possibly of Tie1, predispose individuals to lymphedema and hydrops fetalis (29, 30, 58). This evidence concerns the gene ANGPT2 and hydrops fetalis.