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Sci. Signal., 2 November 2010
Vol. 3, Issue 146, p. re9
[DOI: 10.1126/scisignal.3146re9]


Fibroblast Growth Factor Receptor Signaling Crosstalk in Skeletogenesis

Hichem Miraoui1,2 and Pierre J. Marie1*

1 Laboratory of Osteoblast Biology and Pathology, INSERM UMR606 and University Paris Diderot, Paris 75475, Cedex 10, France.
2 Harvard Reproductive Endocrine Sciences Center and Reproductive Endocrine Unit, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.

Abstract: Fibroblast growth factors (FGFs) play important roles in the control of embryonic and postnatal skeletal development by activating signaling through FGF receptors (FGFRs). Germline gain-of-function mutations in FGFR constitutively activate FGFR signaling, causing chondrocyte and osteoblast dysfunctions that result in skeletal dysplasias. Crosstalk between the FGFR pathway and other signaling cascades controls skeletal precursor cell differentiation. Genetic analyses revealed that the interplay of WNT and FGFR1 determines the fate and differentiation of mesenchymal stem cells during mouse craniofacial skeletogenesis. Additionally, interactions between FGFR signaling and other receptor tyrosine kinase networks, such as those mediated by the epidermal growth factor receptor and platelet-derived growth factor receptor {alpha}, were associated with excessive osteoblast differentiation and bone formation in the human skeletal dysplasia called craniosynostosis, which is a disorder of skull development. We review the roles of FGFR signaling and its crosstalk with other pathways in controlling skeletal cell fate and discuss how this crosstalk could be pharmacologically targeted to correct the abnormal cell phenotype in skeletal dysplasias caused by aberrant FGFR signaling.

* Corresponding author. INSERM U606, Hopital Lariboisiere, 2 rue Ambroise Pare, 75475 Paris cedex 10, France. E-mail: pierre.marie{at}

Citation: H. Miraoui, P. J. Marie, Fibroblast Growth Factor Receptor Signaling Crosstalk in Skeletogenesis. Sci. Signal. 3, re9 (2010).

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