Vascular endothelial growth factors (VEGFs) control angiogenesis and 
lymphangiogenesis during development and in pathological conditions. In the 
zebrafish trunk, Vegfa controls the formation of intersegmental arteries by 
primary angiogenesis and Vegfc is essential for secondary angiogenesis, giving 
rise to veins and lymphatics. Vegfd has been largely thought of as dispensable 
for vascular development in vertebrates. Here, we generated a zebrafish vegfd 
mutant by genome editing. vegfd mutants display significant defects in facial 
lymphangiogenesis independent of vegfc function. Strikingly, we find that vegfc 
and vegfd cooperatively control lymphangiogenesis throughout the embryo, 
including during the formation of the trunk lymphatic vasculature. 
Interestingly, we find that vegfd and vegfc also redundantly drive artery 
hyperbranching phenotypes observed upon depletion of Flt1 or Dll4. Epistasis and 
biochemical binding assays suggest that, during primary angiogenesis, Vegfd 
influences these phenotypes through Kdr (Vegfr2) rather than Flt4 (Vegfr3). 
These data demonstrate that, rather than being dispensable during development, 
Vegfd plays context-specific indispensable and also compensatory roles during 
both blood vessel angiogenesis and lymphangiogenesis.