Tissue-specific responses to aberrant FGF signaling in complex head phenotypes.

[achondroplasia]

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 FGFR 2 c C 3 42 Y mutation is a frequent cause of Crouzon syndrome , characterized by premature cranial vault suture closure , midfacial deficiency , and neurocranial dysmorphology . Here , using newborn Fgfr 2 c (C 3 42 Y /+) 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 .Quantitative analysis of 3 D multimodal imaging (high -resolution micro-computed tomography and magnetic resonance microscopy ) revealed local differences in skull morphology and coronal suture patency between Fgfr 2 c (C 3 42 Y /+) 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 Fgfr 2 c (C 3 42 Y /+) mice .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 .

Diseases
Validation

Diseases presenting "bone development" symptom

achondroplasia

aromatase deficiency

congenital adrenal hyperplasia

dentinogenesis imperfecta

hirschsprung disease

oligodontia

wolf-hirschhorn syndrome

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