Hatch Nan E
Department of Orthodontics and Pediatric Dentistry, University of Michigan, Ann Arbor, MI, USA.
Crit Rev Eukaryot Gene Expr. 2010;20(4):295-311. doi: 10.1615/critreveukargeneexpr.v20.i4.20.
Fibroblast growth factor receptors comprise a family of four evolutionarily conserved transmembrane proteins (FGFR1, FGFR2, FGFR3 and FGFR4) known to be critical for the normal development of multiple organ systems. In this review we will primarily focus upon the role of FGF/FGFR signaling as it influences the development of the craniofacial skeleton. Signaling by FGF receptors is regulated by the tissue-specific expression of FGFR isoforms, receptor subtype specific fibroblast growth factors and heparin sulfate proteoglycans. Signaling can also be limited by the expression of endogenous inhibitors. Gain-of-function mutations in FGFRs are associated with a series of congenital abnormality syndromes referred to as the craniosynostosis syndromes. Craniosynostosis is the clinical condition of premature cranial bone fusion and patients who carry craniosynostosis syndrome-associated mutations in FGFRs commonly have abnormalities of the skull vault in the form of craniosynostosis. Patients may also have abnormalities in the facial skeleton, vertebrae and digits. In this review we will discuss recent in vitro and in vivo studies investigating biologic mechanisms by which signaling through FGFRs influences skeletal development and can lead to craniosynostosis.
成纤维细胞生长因子受体由四种进化上保守的跨膜蛋白（FGFR1、FGFR2、FGFR3和FGFR4）组成，已知对多个器官系统的正常发育至关重要。在本综述中，我们将主要关注FGF/FGFR信号传导在影响颅面骨骼发育方面的作用。FGF受体的信号传导受FGFR亚型的组织特异性表达、受体亚型特异性成纤维细胞生长因子和硫酸乙酰肝素蛋白聚糖的调节。信号传导也可能受到内源性抑制剂表达的限制。FGFRs的功能获得性突变与一系列先天性异常综合征相关，称为颅缝早闭综合征。颅缝早闭是颅骨过早融合的临床病症，携带与颅缝早闭综合征相关突变的FGFRs的患者通常具有以颅缝早闭形式出现的颅顶异常。患者还可能有面部骨骼、椎骨和手指的异常。在本综述中，我们将讨论最近的体外和体内研究，这些研究探讨了通过FGFRs信号传导影响骨骼发育并导致颅缝早闭的生物学机制。
