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The role of Axin2 in calvarial morphogenesis and craniosynostosis

Item Type:Article
Title:The role of Axin2 in calvarial morphogenesis and craniosynostosis
Creators Name:Yu, H.M. and Jerchow, B. and Sheu, T.J. and Liu, B. and Costantini, F. and Puzas, J.E. and Birchmeier, W. and Hsu, W.
Abstract:Axin1 and its homolog Axin2/conductin/Axil are negative regulators of the canonical Wnt pathway that suppress signal transduction by promoting degradation of β-catenin. Mice with deletion of Axin1 exhibit defects in axis determination and brain patterning during early embryonic development. We show that Axin2 is expressed in the osteogenic fronts and periosteum of developing sutures during skull morphogenesis. Targeted disruption of Axin2 in mice induces malformations of skull structures, a phenotype resembling craniosynostosis in humans. In the mutants, premature fusion of cranial sutures occurs at early postnatal stages. To elucidate the mechanism of craniosynostosis, we studied intramembranous ossification in Axin2-null mice. The calvarial osteoblast development is significantly affected by the Axin2 mutation. The Axin2 mutant displays enhanced expansion of osteoprogenitors, accelerated ossification, stimulated expression of osteogenic markers and increases in mineralization. Inactivation of Axin2 promotes osteoblast proliferation and differentiation in vivo and in vitro. Furthermore, as the mammalian skull is formed from cranial skeletogenic mesenchyme, which is derived from mesoderm and neural crest, our data argue for a region-specific effect of Axin2 on neural crest dependent skeletogenesis. The craniofacial anomalies caused by the Axin2 mutation are mediated through activation of {beta}-catenin signaling, suggesting a novel role for the Wnt pathway in skull morphogenesis.
Keywords:Axin, Axin2, Craniosynostosis, Neural Crest, Wnt, Animals, Mice
Source:Development
ISSN:0950-1991
Publisher:Company of Biologists (U.K.)
Volume:132
Number:8
Page Range:1995-2005
Date:1 January 2005
Official Publication:https://doi.org/10.1242/10.1242/dev.01786
PubMed:View item in PubMed

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