Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis

Coussens, A. K., Wilkinson, C. R., Hughes, I. P., Morris, C. P., van Daal, A., Anderson, P. J. and Powell, B. C. (2007) Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis. BMC Genomics, 12 8: 458-466. doi:10.1186/1471-2164-8-458


Author Coussens, A. K.
Wilkinson, C. R.
Hughes, I. P.
Morris, C. P.
van Daal, A.
Anderson, P. J.
Powell, B. C.
Title Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis
Journal name BMC Genomics   Check publisher's open access policy
ISSN 1471-2164
Publication date 2007-01-01
Sub-type Article (original research)
DOI 10.1186/1471-2164-8-458
Open Access Status DOI
Volume 12
Issue 8
Start page 458
End page 466
Total pages 9
Place of publication United Kingdom
Publisher BioMed Central
Language eng
Subject 06 Biological Sciences
0604 Genetics
Abstract Background Craniosynostosis, the premature fusion of calvarial sutures, is a common craniofacial abnormality. Causative mutations in more than 10 genes have been identified, involving fibroblast growth factor, transforming growth factor beta, and Eph/ephrin signalling pathways. Mutations affect each human calvarial suture (coronal, sagittal, metopic, and lambdoid) differently, suggesting different gene expression patterns exist in each human suture. To better understand the molecular control of human suture morphogenesis we used microarray analysis to identify genes differentially expressed during suture fusion in children with craniosynostosis. Expression differences were also analysed between each unfused suture type, between sutures from syndromic and non-syndromic craniosynostosis patients, and between unfused sutures from individuals with and without craniosynostosis. Results We identified genes with increased expression in unfused sutures compared to fusing/fused sutures that may be pivotal to the maintenance of suture patency or in controlling early osteoblast differentiation (i.e. RBP4, GPC3, C1QTNF3, IL11RA, PTN, POSTN). In addition, we have identified genes with increased expression in fusing/fused suture tissue that we suggest could have a role in premature suture fusion (i.e. WIF1, ANXA3, CYFIP2). Proteins of two of these genes, glypican 3 and retinol binding protein 4, were investigated by immunohistochemistry and localised to the suture mesenchyme and osteogenic fronts of developing human calvaria, respectively, suggesting novel roles for these proteins in the maintenance of suture patency or in controlling early osteoblast differentiation. We show that there is limited difference in whole genome expression between sutures isolated from patients with syndromic and non-syndromic craniosynostosis and confirmed this by quantitative RT-PCR. Furthermore, distinct expression profiles for each unfused suture type were noted, with the metopic suture being most disparate. Finally, although calvarial bones are generally thought to grow without a cartilage precursor, we show histologically and by identification of cartilage-specific gene expression that cartilage may be involved in the morphogenesis of lambdoid and posterior sagittal sutures. Conclusion This study has provided further insight into the complex signalling network which controls human calvarial suture morphogenesis and craniosynostosis. Identified genes are candidates for targeted therapeutic development and to screen for craniosynostosis-causing mutations.
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Mon, 12 Apr 2010, 23:20:21 EST by Therese Egan on behalf of Faculty Of Health Sciences