EARLY EXPRESSION OF THE DIFFERENT ISOFORMS OF THE MYOCYTE ENHANCER FACTOR-II (MEF2) PROTEIN IN MYOGENIC AS WELL TPS NONMYOGENIC CELL LINEAGES DURING MOUSE EMBRYOGENESIS

MEF2 proteins are a family of transcription factors that have muscle-s pecific DNA binding activity and bind to conserved A/T rich elements i n the regulatory regions of numerous muscle-specific genes. They are t hought have an important role in the development and differentiation o f skeletal muscle. Recent in situ hybridization studies using mouse ME F2 probes have shown that MEF2 gene transcripts are detected very earl y in development at high levels in the myogenic cells of the myotome a nd embryonic heart. However, MEF2A and MEF2D transcripts have been det ected in many adult tissues where they are not translated or the corre sponding proteins are rapidly degraded. Therefore, it is important to establsh the temporal and spatial correlation between MEF2 RNA and pro tein expression. In the present study we have performed in situ immuno histochemistry of whole mount mouse embryos at different stages of dev elopment using polyclonal antibodies specific for the MEF2A, MEF2C and MEF2D isoforms. At day 8.5 of development, all three MEF2 isoforms ar e expressed in the heart. MEF2A and C are detected in a few cells in t he rostral-most somite by day 9 of development. Their expression then proceeds in a rostro-caudal direction concurrent with somite maturatio n. The pattern of expression of the MEF2D isoform is similar to that o f MEF2C but the amount detected is much lower. Interestingly, MEF2A is also detected as early as day 8.5 p.c. in cells of the embryonic vasc ulature and non-myogenic cells. These results demonstrate that MEF2 pr oteins are detected early in development in the somites and heart, thu s supporting their importance in the early stages of the hierarchical cascade of myogenesis. Their presence in non-muscle cells further sugg ests they could also play a role in the determination of other mesoder mal derivatives, including cells of the vasculature.