Vascular endothelial growth factor (VEGF) and VEGF-C show overlapping binding sites in embryonic endothelia and distinct sites in differentiated adult endothelia

Vascular endothelial growth factor (VEGF) is a key modulator of angiogenesi s during development and in adult tissues, whereas the related VEGF-C has b een shown to induce both lymphangiogenesis and angiogenesis. To better unde rstand the specific functions of these growth factors, we have here analyze d their binding to sections of mouse embryonic and adult tissues and compar ed the distribution of the bound growth factors with the expression pattern s of the 3 known members of the VEGF receptor family as well as with neurop ilin-1, a coreceptor for VEGF(165). Partially overlapping patterns of VEGF and VEGF-C binding were obtained in embryonic tissues, consistent with the expression of all known VEGF receptors by vascular endothelial cells. Howev er, the most striking differences of binding were observed in the developin g and adult heart, in which VEGF decorated all vessels, whereas strong VEGF -C signals were obtained only from epicardial vessels. In the lymph nodes, VEGF and VEGF-C showed distinct binding patterns in agreement with the diff erential location of their specific receptors. These results show that both VEGF-C and VEGF target embryonic blood vessels, whereas a more selective b inding of VEGF-C occurs to its lymphatic vascular receptor in certain adult tissues. Our results suggest that VEGF and VEGF-C have both overlapping an d distinct activities via their endothelial receptors.