Tags

Type your tag names separated by a space and hit enter

Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation.
J Cell Biol. 2005 Mar 28; 168(7):1065-76.JC

Abstract

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 beta-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-beta-catenin pathway.

Authors+Show Affiliations

Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA. mansua01@med.nyu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15781477

Citation

Mansukhani, Alka, et al. "Sox2 Induction By FGF and FGFR2 Activating Mutations Inhibits Wnt Signaling and Osteoblast Differentiation." The Journal of Cell Biology, vol. 168, no. 7, 2005, pp. 1065-76.
Mansukhani A, Ambrosetti D, Holmes G, et al. Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. J Cell Biol. 2005;168(7):1065-76.
Mansukhani, A., Ambrosetti, D., Holmes, G., Cornivelli, L., & Basilico, C. (2005). Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. The Journal of Cell Biology, 168(7), 1065-76.
Mansukhani A, et al. Sox2 Induction By FGF and FGFR2 Activating Mutations Inhibits Wnt Signaling and Osteoblast Differentiation. J Cell Biol. 2005 Mar 28;168(7):1065-76. PubMed PMID: 15781477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. AU - Mansukhani,Alka, AU - Ambrosetti,Davide, AU - Holmes,Greg, AU - Cornivelli,Lizbeth, AU - Basilico,Claudio, Y1 - 2005/03/21/ PY - 2005/3/23/pubmed PY - 2005/6/10/medline PY - 2005/3/23/entrez SP - 1065 EP - 76 JF - The Journal of cell biology JO - J. Cell Biol. VL - 168 IS - 7 N2 - 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 beta-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-beta-catenin pathway. SN - 0021-9525 UR - https://www.unboundmedicine.com/medline/citation/15781477/Sox2_induction_by_FGF_and_FGFR2_activating_mutations_inhibits_Wnt_signaling_and_osteoblast_differentiation_ L2 - https://rupress.org/jcb/article-lookup/doi/10.1083/jcb.200409182 DB - PRIME DP - Unbound Medicine ER -