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The role of Axin2 in calvarial morphogenesis and craniosynostosis.
Development 2005; 132(8):1995-2005D

Abstract

Axin1 and its homolog Axin2/conductin/Axil are negative regulators of the canonical Wnt pathway that suppress signal transduction by promoting degradation of beta-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.

Authors+Show Affiliations

Center for Oral Biology, Department of Biomedical Genetics, Abs Institute of Biomedical Sciences, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15790973

Citation

Yu, Hsiao-Man Ivy, et al. "The Role of Axin2 in Calvarial Morphogenesis and Craniosynostosis." Development (Cambridge, England), vol. 132, no. 8, 2005, pp. 1995-2005.
Yu HM, Jerchow B, Sheu TJ, et al. The role of Axin2 in calvarial morphogenesis and craniosynostosis. Development. 2005;132(8):1995-2005.
Yu, H. M., Jerchow, B., Sheu, T. J., Liu, B., Costantini, F., Puzas, J. E., ... Hsu, W. (2005). The role of Axin2 in calvarial morphogenesis and craniosynostosis. Development (Cambridge, England), 132(8), pp. 1995-2005.
Yu HM, et al. The Role of Axin2 in Calvarial Morphogenesis and Craniosynostosis. Development. 2005;132(8):1995-2005. PubMed PMID: 15790973.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of Axin2 in calvarial morphogenesis and craniosynostosis. AU - Yu,Hsiao-Man Ivy, AU - Jerchow,Boris, AU - Sheu,Tzong-Jen, AU - Liu,Bo, AU - Costantini,Frank, AU - Puzas,J Edward, AU - Birchmeier,Walter, AU - Hsu,Wei, PY - 2005/3/26/pubmed PY - 2005/6/23/medline PY - 2005/3/26/entrez SP - 1995 EP - 2005 JF - Development (Cambridge, England) JO - Development VL - 132 IS - 8 N2 - Axin1 and its homolog Axin2/conductin/Axil are negative regulators of the canonical Wnt pathway that suppress signal transduction by promoting degradation of beta-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. SN - 0950-1991 UR - https://www.unboundmedicine.com/medline/citation/15790973/The_role_of_Axin2_in_calvarial_morphogenesis_and_craniosynostosis_ L2 - http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=15790973 DB - PRIME DP - Unbound Medicine ER -