Fig. 3. A Myod-generated feed-forward circuit temporally patterns gene expression during skeletal muscle differentiation. Myod regulates the transcription of the Mef2 isoforms, including Mef2d, and activates the p38 kinase pathway, shown here mediated by factor X. Factor X might be the Akt2 kinase, which is transcriptionally regulated by Myod and phosphorylates p38. The phosphorylated p38 becomes an active kinase and phosphorylates Mef2d, permitting it to bind and activate the myosin heavy chain (Myh3) gene together with Myod. The Myh3 gene is not activated by Myod until Mef2d is expressed and p38 is active (Penn et al., 2004). The feed-forward mechanism regulates the activity of Myod at a subset of promoters and imposes a temporal order on Myod-mediated gene expression. This diagram uses the graphical language BioD (Cook et al., 2001).