These observations explain well why we did not observe any defects in the lymphatic vessel formation in the VEC-specific Arf6 cKO mice (data not shown), which had been generated previously18, and why the edema was induced in Arf6−/− embryos earlier than in LEC-Arf6 cKO embryos: ablation of Arf6 from both venous and non-venous mesenchymal cells in Arf6−/− embryos might induce the lymphedema earlier than LEC-Arf6-cKO. The gene discussed is ARF6; the disease is lymphedema.