| First Author | McGee-Lawrence ME | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 8 | Pages | 5291-302 |
| PubMed ID | 23300083 | Mgi Jnum | J:196717 |
| Mgi Id | MGI:5489056 | Doi | 10.1074/jbc.M112.414995 |
| Citation | McGee-Lawrence ME, et al. (2013) Runx2 protein represses Axin2 expression in osteoblasts and is required for craniosynostosis in Axin2-deficient mice. J Biol Chem 288(8):5291-302 |
| abstractText | Runx2 and Axin2 regulate craniofacial development and skeletal maintenance. Runx2 is essential for calvarial bone development, as Runx2 haploinsufficiency causes cleidocranial dysplasia. In contrast, Axin2-deficient mice develop craniosynostosis because of high beta-catenin activity. Axin2 levels are elevated in Runx2(-/-) calvarial cells, and Runx2 represses transcription of Axin2 mRNA, suggesting a direct relationship between these factors in vivo. Here we demonstrate that Runx2 binds several regions of the Axin2 promoter and that Runx2-mediated repression of Axin2 transcription depends on Hdac3. To determine whether Runx2 contributes to the etiology of Axin2 deficiency-induced craniosynostosis, we generated Axin2(-/-):Runx2(+/-) mice. These double mutant mice had longer skulls than Axin2(-/-) mice, indicating that Runx2 haploinsufficiency rescued the craniosynostosis phenotype of Axin2(-/-) mice. Together, these studies identify a key mechanistic pathway for regulating intramembranous bone development within the skull that involves Runx2- and Hdac3-mediated suppression of Axin2 to prevent the untimely closure of the calvarial sutures. |
