Fig. 7. Regulation of bone development by MEF2. (A) High-magnification frontal view of Hematoxylin and Eosin-stained sections of mouse sternum. Left, wild-type trabeculated bone. MEF2C KO, chondrocyte-specific deletion of a conditional Mef2c allele, which results in a lack of bone owing to failure in chondrocyte hypertrophy. MEF2-engrailed super-repressor, when expressed in the cartilage of transgenic mice, also prevents ossification, whereas expression of a MEF2-VP16 super-activator results in the formation of excessive bone. (B) MEF2C and MEF2D promote chondrocyte hypertrophy and vascularization of developing bones by activating a network of transcription factors and signaling molecules involved in bone development. HDAC4 imposes negative control over the network by repressing the activity of MEF2 [adapted from Arnold et al. (Arnold et al., 2007)]. IHH, Indian hedgehog; PTHrP, parathyroid hormone-related peptide; RUNX2, runt related transcription factor 2.