Neus Martínez-Abadías, Susan M. Motch, and Joan T. Richtsmeier contributed equally to the manuscript.
Patterns & Phenotypes
Tissue-specific responses to aberrant FGF signaling in complex head phenotypes†
Article first published online: 5 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 242, Issue 1, pages 80–94, January 2013
How to Cite
Martínez-Abadías, N., Motch, S. M., Pankratz, T. L., Wang, Y., Aldridge, K., Jabs, E. W. and Richtsmeier, J. T. (2013), Tissue-specific responses to aberrant FGF signaling in complex head phenotypes. Dev. Dyn., 242: 80–94. doi: 10.1002/dvdy.23903
All authors declare that there are no conflicts of interest.
- Issue published online: 11 DEC 2012
- Article first published online: 5 DEC 2012
- Accepted manuscript online: 21 NOV 2012 12:03PM EST
- Manuscript Accepted: 2 NOV 2012
- Manuscript Revised: 30 OCT 2012
- Manuscript Received: 17 SEP 2012
- NIH. Grant Numbers: R01DE018500, R01DE022988
- NIH and the American Recovery and Reinvestment Act. Grant Number: 3R01DE018500-02S1
- Comissionat per a Universitaats I Recerca (CUR), Generalitat de Catalunya, Spain. Grant Number: 2008 BP A 00170
- Crouzon syndrome;
- Pfeiffer syndrome;
- inner ear
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 Fgfr2cC342Y/+ 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 Fgfr2cC342Y/+ 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 Fgfr2cC342Y/+ 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. Developmental Dynamics 242:80–94, 2013. © 2012 Wiley Periodicals, Inc.