title: Roles of FGF signaling in skeletal development and human genetic diseases.
abstract: Fibroblast growth factor receptors (FGFRs) exist as a gene family of 4 membrane bound receptor tyrosine kinases (FGFR1-4) that mediate signals of at least 22 fibroblast growth factors (FGF1-22). FGFs/FGFRs play important roles in multiple biological processes, including mesoderm induction and patterning, cell growth and migration, organ formation and bone growth. Furthermore, it has been shown that missense mutations of FGFR1-3 in human result in, at least, 14 congential bone diseases that are broadly classified into two groups: chondrodysplasia syndromes and craniosynostosis syndromes. The chondrodysplasia affects primarily the skeleton formed through endochondral ossification, resulting short-limbed dwarfisms, while the craniosynostosis affects mainly bones formed through intramembraneous ossification, leading to premature fusion of the craniofacial sutures. Using gene targeting, mouse models mimicking some of these human diseases have been created. Analysis of these mutant mice revealed essential functions of FGFs/FGFRs in skeletal development and maintenance. These models may be beneficial in future studies aimed at developing novel therapeutic strategies for FGFR-related skeletal dysplasias. In this review, we discuss the results of recent studies on FGF receptors to illustrate mechanisms through which the abnormally activated FGF/FGFR signaling results in these diseases.
authors.affiliation: Trauma Center, Center of Medical Molecular Genetics, Daping Hospital, Third Military Medical University, Daping, Chongqing 400042, China. linchen70@163.com <linchen70@163.com>
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
mesh_terms: D000818:Animals; D005346:Fibroblast Growth Factors / Q000502:physiology*; D030342:Genetic Diseases, Inborn / Q000503:physiopathology; D006801:Humans; D018878:Limb Buds; D051379:Mice; D018482:Muscle, Skeletal / Q000254:growth & development*; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors