Erythroblastic Islands of Fetal Liver of A) Wild-Type and B) EKLF/KLF1 Null Mice. Central macrophages, large gray cells with elongated ovoid nuclei, have cytoplasmic extensions in wild-type but not EKLF/KLF1 null fetal livers. In wild-type central macrophages, EKLF/KLF1 induces DNase IIα, which degrades DNA of phagocytosed apoptotic cells and extruded erythroid nuclei, thereby inhibiting interferon-β (IFN-β) production. In EKLF/KLF1 null central macrophages, EKLF/KLF1 deficiency decreases DNase IIα, which increases undigested DNA, inducing IFN-β production. In wild-type mice, EKLF/KLF1 regulates many genes involved in terminal erythroblast (round nucleated cells) differentiation, including those related to cell division. Consequently, cell size decreases, hemoglobin accumulates (shown as increasingly orange-red cytoplasm), and nuclear condensation and extrusion occur (shown with the extruded nucleus nearby the irregularly shaped, hemoglobin-filled reticulocytes (A). In EKLF/KLF1 null erythroblasts (B), defective terminal differentiation (shown by no orange-red in cytoplasm) due to deficient EKLF/KLF1 combined with increased IFN-β from the central macrophage leads to extensive erythroblast apoptosis (fragmented nuclei) and failure of definitive erythropoiesis.