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Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation

Activating mutations in fibroblast growth factor receptor 2 (FGFR2) cause several craniosynostosis syndromes by affecting the proliferation and differentiation of osteoblasts, which form the calvarial bones. Osteoblasts respond to FGF with increased proliferation and inhibition of differentiation. W...

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Autores principales: Mansukhani, Alka, Ambrosetti, Davide, Holmes, Greg, Cornivelli, Lizbeth, Basilico, Claudio
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171836/
https://www.ncbi.nlm.nih.gov/pubmed/15781477
http://dx.doi.org/10.1083/jcb.200409182
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author Mansukhani, Alka
Ambrosetti, Davide
Holmes, Greg
Cornivelli, Lizbeth
Basilico, Claudio
author_facet Mansukhani, Alka
Ambrosetti, Davide
Holmes, Greg
Cornivelli, Lizbeth
Basilico, Claudio
author_sort Mansukhani, Alka
collection PubMed
description Activating mutations in fibroblast growth factor receptor 2 (FGFR2) cause several craniosynostosis syndromes by affecting the proliferation and differentiation of osteoblasts, which form the calvarial bones. Osteoblasts respond to FGF with increased proliferation and inhibition of differentiation. We analyzed the gene expression profiles of osteoblasts expressing FGFR2 activating mutations (C342Y or S252W) and found a striking down-regulation of the expression of many Wnt target genes and a concomitant induction of the transcription factor Sox2. Most of these changes could be reproduced by treatment of osteoblasts with exogenous FGF. Wnt signals promote osteoblast function and regulate bone mass. Sox2 is expressed in calvarial osteoblasts in vivo and we show that constitutive expression of Sox2 inhibits osteoblast differentiation and causes down-regulation of the expression of numerous Wnt target genes. Sox2 associates with β-catenin in osteoblasts and can inhibit the activity of a Wnt responsive reporter plasmid through its COOH-terminal domain. Our results indicate that FGF signaling could control many aspects of osteoblast differentiation through induction of Sox2 and regulation of the Wnt–β-catenin pathway.
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spelling pubmed-21718362008-03-05 Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation Mansukhani, Alka Ambrosetti, Davide Holmes, Greg Cornivelli, Lizbeth Basilico, Claudio J Cell Biol Research Articles Activating mutations in fibroblast growth factor receptor 2 (FGFR2) cause several craniosynostosis syndromes by affecting the proliferation and differentiation of osteoblasts, which form the calvarial bones. Osteoblasts respond to FGF with increased proliferation and inhibition of differentiation. We analyzed the gene expression profiles of osteoblasts expressing FGFR2 activating mutations (C342Y or S252W) and found a striking down-regulation of the expression of many Wnt target genes and a concomitant induction of the transcription factor Sox2. Most of these changes could be reproduced by treatment of osteoblasts with exogenous FGF. Wnt signals promote osteoblast function and regulate bone mass. Sox2 is expressed in calvarial osteoblasts in vivo and we show that constitutive expression of Sox2 inhibits osteoblast differentiation and causes down-regulation of the expression of numerous Wnt target genes. Sox2 associates with β-catenin in osteoblasts and can inhibit the activity of a Wnt responsive reporter plasmid through its COOH-terminal domain. Our results indicate that FGF signaling could control many aspects of osteoblast differentiation through induction of Sox2 and regulation of the Wnt–β-catenin pathway. The Rockefeller University Press 2005-03-28 /pmc/articles/PMC2171836/ /pubmed/15781477 http://dx.doi.org/10.1083/jcb.200409182 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Mansukhani, Alka
Ambrosetti, Davide
Holmes, Greg
Cornivelli, Lizbeth
Basilico, Claudio
Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation
title Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation
title_full Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation
title_fullStr Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation
title_full_unstemmed Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation
title_short Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation
title_sort sox2 induction by fgf and fgfr2 activating mutations inhibits wnt signaling and osteoblast differentiation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171836/
https://www.ncbi.nlm.nih.gov/pubmed/15781477
http://dx.doi.org/10.1083/jcb.200409182
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