Fig. 2. MEF2 as a central regulator of differentiation and signal responsiveness. MAP kinase signaling activates MEF2. Calcium-dependent signals also activate MEF2 by stimulating calcium-dependent kinases that phosphorylate class II HDACs, thereby promoting their dissociation from MEF2 and derepressing MEF2 target genes. MEF2 recruits numerous co-factors to drive the differentiation of the various cell types shown. Although MAPK and HDAC signaling pathways have been implicated in the modulation of numerous MEF2-dependent developmental programs, these signaling pathways have not yet been shown to operate in all the cell types under MEF2 control.