Developmental biology of erythropoiesis

A newborn infant represents the culmination of developmental events from conception through organogenesis. Red cells are critically important for survival and growth of the embryo. During development, erythropoiesis occurs in two distinct forms. The first 'primitive' form consists of nucleated erythroblasts that differentiate within the blood vessels of the extraembryonic yolk sac. The second 'definitive' form consists of anucleate erythrocytes that differentiate within the liver and third trimester bone marrow of the fetus. While adult bone marrow and cord blood now serve as sources of stem cells for the treatment by transplantation of genetic and malignant diseases, the developmental origin of hematopoietic stem cells has not been determined. During the third trimester the fetus grows rapidly and the production of red cells is approximately 3-5 times that of adult steady state levels. Birth brings dramatic changes in oxygenation and erythropoietin production that result in a tenfold drop in red cell production and in a transient 'physiologic' anemia. Other causes of fetal and infant anemias have their origins in development processes. These include globin gene switching in alpha and beta thalassemia, the expression of red cell antigens in alloimmune hemolytic disease, and the poorly understood defects in the regulation of erythropoiesis in Diamond Blackfan anemia. Even in the adult, vestiges of fetal erythropoiesis are evident during transient states of accelerated erythroid expansion. A better understanding of the development of erythropoiesis will bring improvements in the treatment of anemia, not only in the newborn, but also in the fetus and the adult.