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Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis.
BMC Genomics 2007; 8:458BG

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.

Authors+Show Affiliations

Cooperative Research Centre for Diagnostics, Institute of Health and Biomedical Innovation, Queensland University of Technology,Brisbane 4001, Australia. anna.coussens@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18076769

Citation

Coussens, Anna K., et al. "Unravelling the Molecular Control of Calvarial Suture Fusion in Children With Craniosynostosis." BMC Genomics, vol. 8, 2007, p. 458.
Coussens AK, Wilkinson CR, Hughes IP, et al. Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis. BMC Genomics. 2007;8:458.
Coussens, A. K., Wilkinson, C. R., Hughes, I. P., Morris, C. P., van Daal, A., Anderson, P. J., & Powell, B. C. (2007). Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis. BMC Genomics, 8, p. 458.
Coussens AK, et al. Unravelling the Molecular Control of Calvarial Suture Fusion in Children With Craniosynostosis. BMC Genomics. 2007 Dec 12;8:458. PubMed PMID: 18076769.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unravelling the molecular control of calvarial suture fusion in children with craniosynostosis. AU - Coussens,Anna K, AU - Wilkinson,Christopher R, AU - Hughes,Ian P, AU - Morris,C Phillip, AU - van Daal,Angela, AU - Anderson,Peter J, AU - Powell,Barry C, Y1 - 2007/12/12/ PY - 2007/09/11/received PY - 2007/12/12/accepted PY - 2007/12/14/pubmed PY - 2008/3/8/medline PY - 2007/12/14/entrez SP - 458 EP - 458 JF - BMC genomics JO - BMC Genomics VL - 8 N2 - 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. SN - 1471-2164 UR - https://www.unboundmedicine.com/medline/citation/18076769/Unravelling_the_molecular_control_of_calvarial_suture_fusion_in_children_with_craniosynostosis_ L2 - https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-8-458 DB - PRIME DP - Unbound Medicine ER -