1. β-catenin/cyclin D1 mediated development of suture mesenchyme in calvarial morphogenesis
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Hsiao-Man Ivy Yu, Wei-Chun Hsu, Anthony J. Mirando, Jiang Fu, and Takamitsu Maruyama
- Subjects
Mesoderm ,Beta-catenin ,Mesenchyme ,Morphogenesis ,Mice, Transgenic ,Biology ,Bone morphogenetic protein ,Fibroblast growth factor ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cyclin D1 ,Axin Protein ,medicine ,Animals ,Cell Lineage ,lcsh:QH301-705.5 ,Cells, Cultured ,beta Catenin ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Osteoblasts ,Stem Cells ,Skull ,Cranial Sutures ,Molecular biology ,Cell biology ,Fibroblast Growth Factors ,Wnt Proteins ,Cytoskeletal Proteins ,medicine.anatomical_structure ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Catenin ,Bone Morphogenetic Proteins ,biology.protein ,Biomarkers ,Research Article ,Signal Transduction ,Developmental Biology - Abstract
Background Mouse genetic study has demonstrated that Axin2 is essential for calvarial development and disease. Haploid deficiency of β-catenin alleviates the calvarial phenotype caused by Axin2 deficiency. This loss-of-function study provides evidence for the requirement of β-catenin in exerting the downstream effects of Axin2. Results Here we utilize a gain-of-function analysis to further assess the role of β-catenin. A transgenic expression system permitting conditional activation of β-catenin in a spatiotemporal specific manner has been developed. Aberrant stimulation of β-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. β-catenin signaling apparently plays a key role in suture development through modulation of calvarial morphogenetic signaling pathways. Furthermore, genetic inactivation of the β-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/β-catenin/cyclin D1 in development of the suture mesenchyme.
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