Shear tango: dance of the ADAMTS13/VWF complex.

cooperate with VEGFR-3 in lymphatic endothe-lial cell migration and proliferation. Whereas VEGF-C is essential in mouse lymphatic vascu-lar development, it remains to be resolved to what extent the lack of VEGFR-2 binding accounts for the dispensable role of VEGF-D in this process. 5,6 Elucidation of the receptor-binding pattern of Xenopus VEGF-D and finding whether it explains the functional difference between VEGF-C and VEGF-D in this organism might bring us a step forward in solving this question. A hint to the lymphangiogenic modi-fier role of VEGF-D is provided by the fact that exogenous VEGF-D protein administration is able to partially rescue the impaired sprouting and migration of lymphatic endothelial cells in VEGF-C– deficient mouse embryos, 6 although loss of endogenous VEGF-D does not aggravate the VEGF-C null phenotype. 7 Death of VEGFR-3– deficient mice due to blood vascular defects prior to lymphatic vessel development has precluded studies of the role of VEGFR-3 in mouse embryonic lym-phangiogenesis. 8 The importance of VEGFR-3 signaling in embryonic lymphatic vascular development, postnatal lymphatic vessel survival, and stimulation of adult lym-phangiogenesis has been directly or indirectly demonstrated in various experimental settings in several species. By using genetic down-regulation and chemical inhibition, Ny et al document the critical role of VEGFR-3 in developmental lymphangiogenesis in the Xe-nopus tadpole model and thus the functional conservation of VEGFR-3 in this species. A profound understanding of the molecular regulation of lymphatic vascular development and the entire range of functions of its major players and modifiers should enable the development of controlled antilymphangio-genic and prolymphangiogenic therapies. Characterization of the lymphatic system in small model organisms has provided new tools to study lymphangiogenic processes and to complement the methods available in mammals. Ny et al highlight the potential of Xeno-pus tadpoles in lymphatic vascular research by demonstrating the subtle modifier role of VEGF-D in lymphatic vascular development. Conflict-of-interest disclosure: T.K. declares no competing financial interests. K.A. is a minority shareholder of Lymphatix Ltd. and the Chairman of the Scientific Advisory Board of Vegenics Ltd. ■ REFERENCES 1. Veikkola T, Jussila L, Makinen T, et al. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J. VEGF-D is the strongest angiogenic and lymphangiogenic effector among VEGFs delivered into skeletal muscle via adenoviruses.thelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. ADAMTS13, the metalloprotease that regulates the size of von Willebrand …