Ontogeny of Mammalian Hematopoiesis The first blood cells in the mammalian embryo emerge within yolk sac blood islands from hemangioblast precursors (Huber, et al. Nature, 2004). Also in collaboration with the laboratory of Gordon Keller, we identified two waves of hematopoietic progenitors emerging from the yolk sac prior to colonization of the liver (Palis, et al. Development, 1999). The first “primitive” wave is at least bilineage in nature, since it contains both primitive erythroid and megakaryocyte progenitors (Tober, et al. Blood, 2007). The second “definitive” wave contains definitive erythroid, megakaryocyte, and multiple myeloid lineages (Palis, et al. Proc Natl Acad Science, 2001). The lineage composition and relationships of these primitive and definitive progenitor waves and their contribution to hematopoiesis in the fetal liver are under active investigation. Taken together, our studies indicate that the onset of hematopoiesis within the yolk sac of mammals is much more complex than previously thought. Immunohistochemical staining with anti-bH1-globin (blue) and anti-GP1bb (red) antibodies identifies a colony derived from a bipotential megakaryocyte/primitive erythroid progenitor derived from the murine yolk sac. References Palis J, Kennedy M, Robertson S, Wall C, Keller G: Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse embryo. Development 126:5073-5084, 1999. Palis J, Chan RJ, Koniski A, Patel R, Starr M, Yoder MC: Spatial and temporal emergence of high proliferative potential hematopoietic precursors during murine embryogenesis. Proceedings National Academy of Science USA 98:4528-4533, 2001. Huber TL, Kouskoff V, Fehling HJ, Palis J, Keller G. Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature 432:625-630, 2004. Tober J, Koniski A, McGrath KE, Vemishetti R, Emerson R, de Mesy-Bentley KKL, Waugh R, Palis J: The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and definitive hematopoiesis. Blood 109:1433-1441, 2007. Kingsley PD, Greenfest-Allen E, Frame JM, Bushnell TP, Malik J, McGrath KE, Stoeckert CJ Jr, Palis J. Ontogeny of erythroid gene expression. Blood 121:e5-e13, 2013.