Vegfd, a member of the VEGF family, is implicated in angiogenesis and lymphangiogenesis [1]. It also plays a role in maintaining the structural integrity of dendrites in the nervous system, balancing their stability and activity-dependent plasticity [2]. In addition, Vegfd is involved in blood vascular development by modulating SOX18 activity [4]. Zebrafish and mouse models have been crucial for studying its functions [3,4].

In zebrafish, vegfd mutants display defects in facial lymphangiogenesis, and vegfd cooperates with vegfc to control lymphangiogenesis throughout the embryo. It can also compensate for the loss of vegfc in facial lymphatic sprouting. Moreover, vegfd influences artery hyperbranching phenotypes through Kdr during primary angiogenesis [3,6]. In mice, Sox18/Vegfd double knockout mice show dramatic vascular development defects, indicating an interaction between Vegfd and Sox18 in arteriovenous differentiation [4]. Additionally, in ischemic stroke models, VEGFD/VEGFR3 signaling contributes to the dysfunction of the astrocyte IL-3/microglia IL-3Rα cross-talk and drives neuroinflammation [5].

In conclusion, Vegfd is essential for angiogenesis, lymphangiogenesis, and maintaining dendritic and vascular integrity. Gene knockout models in zebrafish and mice have revealed its role in these processes and in diseases like ischemic stroke, providing insights into potential therapeutic strategies targeting Vegfd-related pathways.