CLEC-2 is required in blood cells for normal lymphatic vascular development. (A-L) Clec-2^−/− animals exhibit blood-lymphatic vascular mixing phenotypes. (A-F) Clec-2^−/− embryos exhibit blood-filled lymphatics like those of Slp-76^−/− animals during mid-gestation. Whole embryo images show blood-filled cutaneous lymphatics and edema (above). Transverse sections show anti-LYVE-1 immunostaining (brown) of lymph sacs adjacent to the cardinal vein (below). (G-L) Clec-2^−/− neonates exhibited blood-filled mesenteric vessels (G,I,K) and edema of the intestine wall (H,J,L) like those of Slp-76^−/− animals. (M-O) Blood-filled mesenteric lymphatic vessels arise in lethally irradiated wild-type mice after reconstitution with Clec-2^−/− (N-O) but not wild-type (M) donor hematopoietic cells. A indicates artery; V, vein; and L, lymphatic.