Ontogeny of erythropoiesis in the mammalian embryo

Red cells are required not only for adult well-being but also for survival and growth of the mammalian embryo beyond early postimplantation stages of development. The embryo's first "primitive" erythroid cells, derived from a transient wave of committed progenitors, emerge from the yolk sac as immature precursors and differentiate as a semisynchronous cohort in the bloodstream. Surprisingly, this maturational process in the mammalian embryo is characterized by globin gene switching and ultimately by enucleation. The yolk sac also synthesizes a second transient wave of "definitive" erythroid progenitors that enter the bloodstream and seed the liver of the fetus. At the same time, hematopoietic stem cells within the embryo also seed the liver and are the presumed source of long-term erythroid potential. Fetal definitive erythroid precursors mature in macrophage islands within the liver, enucleate, and enter the bloodstream as erythrocytes. Toward the end of gestation, definitive erythropoiesis shifts to its final location, the bone marrow. It has recently been recognized that the yolk sac-derived primitive and fetal definitive erythroid lineages, like their adult definitive erythroid counterpart, are each hierarchically associated with the megakaryocyte lineage. Continued comparative studies of primitive and definitive erythropoiesis in mammalian and nonmammalian embryos will lead to an improved understanding of terminal erythroid maturation and globin gene regulation.