Role of EKLF in erythroid lineage development. At the MEP stage, EKLF represses megakaryopoiesis while at the same time it promotes erythropoiesis. This process likely relies, at least in part, on cross-antagonizing interactions between EKLF and Fli-1, a crucial megakaryocyte transcription factor. Committed erythrocyte progenitors expand through renewal divisions that occur during fetal erythropoiesis or after hypoxic stress.66 Terminal maturation of erythrocytes occurs throughout differentiation divisions, where cells undergo many changes: size reduction, hemoglobin accumulation, decrease in overall gene expression level, nuclear condensation, and ultimate extrusion. These events are particularly dependent on the presence of, and in some cases, the level of EKLF. The inset shows the progression of erythroid development in WT and EKLF-deficient fetal liver cells as monitored by presence of the cell-surface markers CD71 and Ter119. Discrete populations of cells (R1-R5) with distinct morphologies can be distinguished, which correspond to particular stages of cells during erythropoiesis, as described in “Dual role of EKLF in establishing lineage fate.” (Used with permission from Pilon et al.34 )