Model of the differential requirements for GATA-1 in megakaryocyte gene expression and development. Committed megakaryocyte progenitors (A) normally display limited proliferation. However, in the absence of GATA-1, or in the presence of GATA-1s, these progenitors hyperproliferate and produce a greater number of CD41⁺ megakaryocytes, which also express low levels of CD42 (B). In contrast, when the ability of GATA-1 to interact with FOG-1 is disrupted, progenitors expand to a lesser degree. Megakaryocytes then undergo repeated rounds of DNA synthesis without cell division (polyploidization) to generate a polyploid cell (C). Mutagenesis of GATA-1 did not affect the endomitosis of megakaryocytes. However, alterations in GATA-1 led to differential effects on terminal maturation. In the absence of GATA-1, or in the presence of the V205G mutant, terminal maturation was blocked. When GATA-1s was expressed, however, megakaryocytes produced proplatelet forms (D) and were similar to wild-type cells in morphology and gene expression.