Model: a putative role for macrophages in the homeostatic response to hypoxia, based on in vitro analyses. In response to hypoxia, we propose that erythroblasts lose their tight adherence to central macrophages of erythroblastic islands, possibly promoting unrestrained maturation of erythroid progenitors, and increasing the number of red cells getting into the circulation. This may also promote the migration of immature erythroid progenitors to organs such as the spleen where their expansion is enhanced under stress conditions.³¹  In the Rb-null embryo, severe hypoxia and fetal liver necrosis disrupt erythropoietic islands concomitant with, but independent of, red cell enucleation defects and embryonic lethality.