Laboratory of Osteoblast Biology and Pathology, INSERM UMR606 and University Paris Diderot, Paris 75475, Cedex 10, France.
Sci Signal. 2010 Nov 2;3(146):re9. doi: 10.1126/scisignal.3146re9.
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 α, 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.
成纤维细胞生长因子（FGFs）通过激活 FGF 受体（FGFRs）的信号通路，在胚胎期和出生后骨骼发育的调控中发挥重要作用。FGFR 中的种系获得性功能突变持续激活 FGFR 信号通路，导致软骨细胞和成骨细胞功能障碍，从而导致骨骼发育不良。FGFR 通路与其他信号级联之间的串扰控制骨骼前体细胞的分化。遗传分析表明，WNT 和 FGFR1 的相互作用决定了小鼠颅面骨骼发生过程中间充质干细胞的命运和分化。此外，FGFR 信号与其他受体酪氨酸激酶网络（如表皮生长因子受体和血小板衍生生长因子受体α介导的网络）之间的相互作用与人类骨骼发育不良称为颅缝早闭症中的成骨细胞过度分化和骨形成有关，这是一种颅骨发育障碍。我们综述了 FGFR 信号及其与其他通路相互作用在控制骨骼细胞命运中的作用，并讨论了如何通过药理学靶向这种相互作用来纠正异常 FGFR 信号引起的骨骼发育不良中的异常细胞表型。
