Proposed model of Mef2C regulation and function in hematopoiesis. Unlike Scl, which is absolutely required for the specification of mesoderm to blood and emergence of HSCs, Mef2C is not essential for hematopoietic specification, although it remains unclear why definitive hematopoiesis specifically in the embryo proper is impaired. It is plausible that the defects in vascular, muscle, and cardiac differentiation observed in Mef2C^−/− embryos may indirectly affect hematopoiesis in the embryo proper. In the adult, we discovered novel requirements for Mef2C in 2 hematopoietic lineages. Our data indicate that, in the megakaryocytic lineage, Mef2C is a direct target gene of Scl and, as Scl, is required for proper megakaryopoiesis and platelet biogenesis. In contrast, although Scl is required for erythroid differentiation, Scl does not activate Mef2C in erythroid cells. In B cells, where Scl is not expressed, Mef2C probably acts downstream of other bHLH factors (eg, E12/E47) to counteract B-lymphocyte aging, especially within the pre–B-cell fraction. Finally, Mef2C was recently shown to be expressed in myeloid cells where it acts to modulate myeloid cell fates.⁴⁴  Text in red indicates expression and cell-intrinsic functional requirement in the specific lineage, whereas gray text indicates expression in tissues in which cell-intrinsic functional requirement of Mef2C in hematopoietic cells has not been documented. HSC indicates hematopoietic stem cell; MPP, multipotent progenitor; CLP, common lymphoid progenitor; CMP, common myeloid progenitor; Meg, megakaryocyte; and Ery, erythroid progenitor.