A hierarchy of transcription factors important in megakaryopoiesis. The normal progression of a multipotential progenitor to a platelet-producing megakaryocyte (MK) is shown. The upper set of arrows denotes the normal pattern of progression from one cell type to another, and the lower set of arrows illustrates the findings in a GATA-1–deficient environment. The thickness of the arrows represents the degree to which the progression from 1 cell type to another occurs. In GATA-1 deficiency, there is a marked increase of immature megakaryocytes relative to the wild type. Most normal immature megakaryocytes complete differentiation, whereas in GATA-1 deficiency, many immature megakaryocytes fail to complete the differentiation program, and the few that do are abnormal structurally. This results in a lower number of circulating platelets that are functionally and structurally abnormal. In the absence of FOG, either the megakaryocyte progenitor is not specified or fails to differentiate. Conversely, the requirement for NF-E2 is apparently limited to terminal megakaryocyte differentiation before platelet release.