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 "growth factor" symptom

22q11.2 deletion syndrome

achondroplasia

adrenal incidentaloma

aniridia

cadasil

cholangiocarcinoma

coats disease

dedifferentiated liposarcoma

dentin dysplasia

dentinogenesis imperfecta

dystrophic epidermolysis bullosa

esophageal carcinoma

esophageal squamous cell carcinoma

hodgkin lymphoma, classical

holt-oram syndrome

inclusion body myositis

kallmann syndrome

krabbe disease

liposarcoma

lymphangioleiomyomatosis

oculocutaneous albinism

oral submucous fibrosis

pleomorphic liposarcoma

primary effusion lymphoma

primary hyperoxaluria type 1

severe combined immunodeficiency

systemic capillary leak syndrome

von hippel-lindau disease

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

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