Summary
Apert syndrome is an autosomal dominant disorder characterized by malformations of the skull, limbs and viscera. Two-thirds of affected individuals have a S252W mutation in fibroblast growth factor receptor 2 (FGFR2). To study the pathogenesis of this condition, we generated a knock-in mouse model with this mutation. The Fgfr2+/S252W mutant mice have abnormalities of the skeleton, as well as of other organs including the brain, thymus, lungs, heart and intestines. In the mutant neurocranium, we found a midline sutural defect and craniosynostosis with abnormal osteoblastic proliferation and differentiation. We noted ectopic cartilage at the midline sagittal suture, and cartilage abnormalities in the basicranium, nasal turbinates and trachea. In addition, from the mutant long bones, in vitro cell cultures grown in osteogenic medium revealed chondrocytes, which were absent in the controls. Our results suggest that altered cartilage and bone development play a significant role in the pathogenesis of the Apert syndrome phenotype.
- Apert syndrome
- Fibroblast growth factor receptor 2
- Mouse
- Cartilage
- Bone
- Mesenchyme
- Neural crest
- Skull
- Suture
- Craniosynostosis
Footnotes
-
Supplementary material
-
Supplementary material for this article is available at http://dev.biologists.org/cgi/content/full/132/15/3537/DC1
-
↵* These authors contributed equally to this work
- Accepted May 13, 2005.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Other journals from The Company of Biologists
Kathryn Virginia Anderson (1952-2020)
Developmental geneticist Kathryn Anderson passed away at home on 30 November 2020. Tamara Caspary, a former postdoc and friend, remembers Kathryn and her remarkable contribution to developmental biology.
Zooming into 2021
In a new Editorial, Editor-in-Chief James Briscoe and Executive Editor Katherine Brown reflect on the triumphs and tribulations of the last 12 months, and look towards a hopefully calmer and more predictable year.
Read & Publish participation extends worldwide
Over 60 institutions in 12 countries are now participating in our Read & Publish initiative. Here, James Briscoe explains what this means for his institution, The Francis Crick Institute. Find out more and view our full list of participating institutions.
Upcoming special issues
Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021
The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022
Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.
Development presents...
Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Sign up to join our next session:
10 February
Time: 13:00 (GMT)
Chaired by: preLights