title: Tissue-specific responses to aberrant FGF signaling in complex head phenotypes.
abstract: BACKGROUND
  The role of fibroblast growth factor and receptor (FGF/FGFR) signaling in bone development is well studied, partly because mutations in FGFRs cause human diseases of achondroplasia and FGFR-related craniosynostosis syndromes including Crouzon syndrome. The FGFR2c C342Y mutation is a frequent cause of Crouzon syndrome, characterized by premature cranial vault suture closure, midfacial deficiency, and neurocranial dysmorphology. Here, using newborn Fgfr2c(C342Y/+) Crouzon syndrome mice, we tested whether the phenotypic effects of this mutation go beyond the skeletal tissues of the skull, altering the development of other non-skeletal head tissues including the brain, the eyes, the nasopharynx, and the inner ears.
  
  
  RESULTS
  Quantitative analysis of 3D multimodal imaging (high-resolution micro-computed tomography and magnetic resonance microscopy) revealed local differences in skull morphology and coronal suture patency between Fgfr2c(C342Y/+) mice and unaffected littermates, as well as changes in brain shape but not brain size, significant reductions in nasopharyngeal and eye volumes, and no difference in inner ear volume in Fgfr2c(C342Y/+) mice.
  
  
  CONCLUSIONS
  These findings provide an expanded catalogue of clinical phenotypes in Crouzon syndrome caused by aberrant FGF/FGFR signaling and evidence of the broad role for FGF/FGFR signaling in development and evolution of the vertebrate head.
authors.affiliation: Department of Anthropology, Pennsylvania State University, University Park, PA, USA.
authors.forename: Neus
authors.initials: N
authors.lastname: Martínez-Abadías
authors.forename: Susan M
authors.initials: SM
authors.lastname: Motch
authors.forename: Talia L
authors.initials: TL
authors.lastname: Pankratz
authors.forename: Yingli
authors.initials: Y
authors.lastname: Wang
authors.forename: Kristina
authors.initials: K
authors.lastname: Aldridge
authors.forename: Ethylin Wang
authors.initials: EW
authors.lastname: Jabs
authors.forename: Joan T
authors.initials: JT
authors.lastname: Richtsmeier
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D003393:Cranial Sutures / Q000473:pathology; D003394:Craniofacial Dysostosis / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D012886:Skull / Q000473:pathology*; D055114:X-Ray Microtomography
chemical_list: D051497:Receptor, Fibroblast Growth Factor, Type 2