| First Author | Mirando AJ | Year | 2010 |
| Journal | BMC Dev Biol | Volume | 10 |
| Pages | 116 | PubMed ID | 21108844 |
| Mgi Jnum | J:166753 | Mgi Id | MGI:4849572 |
| Doi | 10.1186/1471-213X-10-116 | Citation | Mirando AJ, et al. (2010) beta-catenin/cyclin D1 mediated development of suture mesenchyme in calvarial morphogenesis. BMC Dev Biol 10:116 |
| abstractText | BACKGROUND: Mouse genetic study has demonstrated that Axin2 is essential for calvarial development and disease. Haploid deficiency of beta-catenin alleviates the calvarial phenotype caused by Axin2 deficiency. This loss-of-function study provides evidence for the requirement of beta-catenin in exerting the downstream effects of Axin2. RESULTS: Here we utilize a gain-of-function analysis to further assess the role of beta-catenin. A transgenic expression system permitting conditional activation of beta-catenin in a spatiotemporal specific manner has been developed. Aberrant stimulation of beta-catenin leads to increases in expansion of skeletogenic precursors and the enhancement of bone ossification reminiscent to the loss of Axin2. The constitutively active signal promotes specification of osteoprogenitors, but prevents their maturation into terminally differentiated osteoblasts, along the osteoblast lineage. However, the prevention does not interfere with bone synthesis, suggesting that mineralization occurs without the presence of mature osteoblasts. beta-catenin signaling apparently plays a key role in suture development through modulation of calvarial morphogenetic signaling pathways. Furthermore, genetic inactivation of the beta-catenin transcriptional target, cyclin D1, impairs expansion of the skeletogenic precursors contributing to deficiencies in calvarial ossification. There is a specific requirement for cyclin D1 in populating osteoprogenitor cell types at various developmental stages. CONCLUSION: These findings advance our knowledge base of Wnt signaling in calvarial morphogenesis, suggesting a key regulatory pathway of Axin2/beta-catenin/cyclin D1 in development of the suture mesenchyme. |
