FIGURE 1.

Microglial ontogeny models. (A) Mouse: Primitive hematopoiesis in the embryonic yolk sac blood islands at E7.5–E8.0 results in the formation of not just erythrocytes but also highly proliferative macrophage progenitor cells that migrate to the brain. The primitive macrophages colonizing the early developing brain at E8.5 proliferate and give rise to the brain-resident microglia population. A second wave, the transient definitive hematopoiesis in the yolk sac, gives rise to erythromyeloid progenitor cells by E8.0–E8.5 and to T- and B-lymphoid progenitor cells by E9.0. On reaching the fetal liver by E10.5, these cells undergo definitive hematopoiesis to result in the formation of all hematopoietic lineage cells, including monocytes. Recent studies now indicate that definitive hematopoiesis also partly contribute to the brain resident microglia population through hoxb8⁺ and CCR2⁺ monocyte populations taking up residence in the early developing brain parenchyma by E12.5 and E17.0, respectively. (B) Zebrafish: Embryonic microglia originating in the rostral blood islands through primitive hematopoiesis by 4 dpf migrates to and populates the embryonic brain until 15 dpf, they disappear entirely by 45 dpf. In essence, the embryonic microglia are replaced by another wave of incoming microglia that arise as a result of definitive hematopoiesis occurring in the ventral walls of the dorsal aorta beginning at 15 dpf. They are the dominant microglia population by 45 dpf and serve as adult microglia throughout the fish’s life.