During mouse embryogenesis, blood cells develop in close association with endothelial cells. The close temporal and spatial association between hematopoietic and endothelial cells has led to the hypothesis that they share a common progenitor, the hemangioblast. Specifically, gene targeting studies and in vitro differentiation models of embryonic stem (ES) cells have been instrumental in identifying genes critical for hematopoietic and endothelial cell lineage differentiation. The first mature blood cells, known as primitive erythrocytes, are produced from the extraembryonic tissue, the yolk sac. Mesodermal cells that have migrated from the primitive streak colonize the presumptive yolk sac at approximately embryonic day (E) and aggregate to form blood islands. The close developmental association of the hematopoietic and endothelial cells within yolk sac blood islands has led to the hypothesis that they arise from a common precursor, the hemangioblast. Similarly, blood cells of the embryo proper develop in close association with the endothelium of the dorsal aorta. Major arteries, such as the vitelline and umbilical arteries of embryos have also been reported to associate with emerging blood cells. In contrast to the common progenitor concept in the yolk sac, blood cells in the embryo proper are believed to differentiate from the endothelium. For example, at the base of the dorsal aorta of the chicken or quail intra-aortic CD45+VEGFR-2 (Flk-1), hematopoietic cells appear to develop from VEGFR-2+ (Flk-1+) cells that take up DiI-conjugated acetylated low-density lipoprotein (DiI-Ac-LDL).