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FGF gets in your bones

Sox2 prevents the differentiation of osteoblasts at the osteogenic front (of).

Wnt-mediated differentiation of bone precursors gets shut down, say Mansukhani et al. on page 1065, if there is too much FGF receptor (FGFR) activity.Bones form through the maturation of osteoblasts. This process is disrupted in the skulls of patients with activating mutations in FGFR1 and FGFR2. The new evidence suggests that FGF counteracts differentiation by blocking Wnt. Microarray analysis revealed that, although Wnt-regulated genes are normally turned on in maturing osteoblasts, their activation is dampened in the overactive FGFR mutant osteoblasts.

A major mediator of the FGF-induced Wnt down-regulation seems to be the Sox2 transcription factor. Normally associated with neurons or embryonic stem cells, Sox2 is now shown to be strongly expressed in osteoblasts when FGF signaling is high. Sox2 was associated with ß-catenin in osteoblasts and blocked Wnt signaling, possibly by competing with other ß-catenin partners, such as TCF/LEF transcriptional coactivators.

Wnt signals are used in multiple differentiation pathways, including several that are not blocked by FGF. Perhaps Sox2 is permanently silenced in the unaffected cell types. It will now be important to examine FGF and Sox2 regulation in normal and pathological skull development. Sox2 was found at osteogenic fronts in mice crania, where FGFR2 activity is known to be high, and may act as a brake on osteoblast differentiation. Harmonious bone formation, like other developmental processes, probably results from the interplay between positive and negative signals.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Related Article

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

Alka Mansukhani, Davide Ambrosetti, Greg Holmes, Lizbeth Cornivelli, and Claudio Basilico
J. Cell Biol. 2005 168: 1065-1076. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 655K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?