| First Author | Arnold MA | Year | 2007 |
| Journal | Dev Cell | Volume | 12 |
| Issue | 3 | Pages | 377-89 |
| PubMed ID | 17336904 | Mgi Jnum | J:119152 |
| Mgi Id | MGI:3701381 | Doi | 10.1016/j.devcel.2007.02.004 |
| Citation | Arnold MA, et al. (2007) MEF2C transcription factor controls chondrocyte hypertrophy and bone development. Dev Cell 12(3):377-89 |
| abstractText | Chondrocyte hypertrophy is essential for endochondral bone development. Unexpectedly, we discovered that MEF2C, a transcription factor that regulates muscle and cardiovascular development, controls bone development by activating the gene program for chondrocyte hypertrophy. Genetic deletion of Mef2c or expression of a dominant-negative MEF2C mutant in endochondral cartilage impairs hypertrophy, cartilage angiogenesis, ossification, and longitudinal bone growth in mice. Conversely, a superactivating form of MEF2C causes precocious chondrocyte hypertrophy, ossification of growth plates, and dwarfism. Endochondral bone formation is exquisitely sensitive to the balance between MEF2C and the corepressor histone deacetylase 4 (HDAC4), such that bone deficiency of Mef2c mutant mice can be rescued by an Hdac4 mutation, and ectopic ossification in Hdac4 null mice can be diminished by a heterozygous Mef2c mutation. These findings reveal unexpected commonalities in the mechanisms governing muscle, cardiovascular, and bone development with respect to their regulation by MEF2 and class II HDACs. |
