FIGURE 1.

Fetal Macrophage Development. Murine macrophages originate from three successive waves of hematopoiesis. The first wave, termed primitive hematopoiesis, occurs in the blood islands of the extra-embryonic yolk sac at E7.5. It produces primitive erythroblasts and megakaryocytes, as well as CSF-1R⁺ c-Myb^- progenitors, which give rise to adult microglia in the brain. The second wave arises from the hemogenic endothelium formed at E8.5 in the yolk sac. Because the second wave generates the c-Myb⁺ hematopoietic progenitors named eythro-myeloid precursors (EMP), thus it is termed the EMP wave. The EMP either give rise to yolk sac macrophages locally or migrate into the fetal liver through the blood circulation, where they expand and differentiate into tissue-resident macrophages, which then migrate to, and colonize, different tissues. The third wave arises from the hemogenic endothelium in the aorta-gonad-mesonephros (AGM) region, which gives rise to fetal hematopoietic stem and progenitor cells beginning at E9.5. Subsequently, these precursors colonize the fetal liver where they establish definitive hematopoiesis and will eventually seed the bone marrow and lead to the generation of adult hematopoietic stem and progenitor cells.