期刊
DEVELOPMENTAL BIOLOGY
卷 301, 期 1, 页码 298-308出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2006.10.018
关键词
Axin; Wnt; beta-catenin; BMP; craniosynostosis; skull; suture; craniofacial morphogenesis; development abnormalities
资金
- NATIONAL CANCER INSTITUTE [R01CA106308] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE015654] Funding Source: NIH RePORTER
- NCI NIH HHS [R01 CA106308, CA106308] Funding Source: Medline
- NIDCR NIH HHS [DE015654, R01 DE015654] Funding Source: Medline
Targeted disruption of Axin2 in mice induces skeletal defects, a phenotype resembling craniosynostosis in humans. Premature fusion of cranial sutures, caused by deficiency in intramembranous ossification, occurs at early postnatal stages. Axin2 negatively regulates both expansion of osteoprogenitors and maturation of osteoblasts through its modulation on Wnt/beta-catenin signaling. We investigate the dual role of beta-catenin to gain further insights into the skull morphogenetic circuitry. We show that as a transcriptional co-activator, beta-catenin promotes cell division by stimulating its target cyclin D1 in osteoprogenitors. Upon differentiation of osteoprogenitors, BMP signaling is elevated to accelerate the process in a positive feedback mechanism. This Writ-dependent BMP signal dictates cellular distribution of beta-catenin. As an adhesion molecule, beta-catenin promotes cell-cell interaction mediated by adherens junctions in mature osteoblasts. Finally, haploid deficiency of beta-catenin alleviates the Axin2-null skeletal phenotypes. These findings support a model for disparate roles of beta-catenin in osteoblast proliferation and differentiation. (c) 2006 Elsevier Inc. All rights reserved.
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