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Spatial regulation of gene expression in nonsyndromic sagittal craniosynostosis.
J Neurosurg Pediatr 2018; 22(6):620-626JN

Abstract

OBJECTIVE

Cranial suture patterning and development are highly regulated processes that are not entirely understood. While studies have investigated the differential gene expression for different sutures, little is known about gene expression changes during suture fusion. The aim of this study was to examine gene expression in patent, fusing, and fused regions along sagittal suture specimens in nonsyndromic craniosynostosis patients.

METHODS

Sagittal sutures were collected from 7 patients (average age 4.5 months) who underwent minimally invasive craniotomies at the Children's Hospital of Richmond at VCU under IRB approval. The sutures were analyzed using micro-CT to evaluate patency. The areas were classified as open, fusing, or fused and were harvested, and mRNA was isolated. Gene expression for bone-related proteins, osteogenic and angiogenic factors, transforming growth factor-β (TGF-β) superfamily, and Wnt signaling was analyzed using quantitative polymerase chain reaction and compared with normal sutures collected from fetal demise tissue (control).

RESULTS

Micro-CT demonstrated that there are variable areas of closure along the length of the sagittal suture. When comparing control samples to surgical samples, there was a significant difference in genes for Wnt signaling, TGF-β, angiogenic and osteogenic factors, bone remodeling, and nuclear rigidity in mRNA isolated from the fusing and fused areas of the sagittal suture compared with patent areas (p < 0.05).

CONCLUSIONS

In nonsyndromic sagittal craniosynostosis, the affected suture has variable areas of being open, fusing, and fused. These specific areas have different mRNA expression. The results suggest that BMP-2, FGFR3, and several other signaling pathways play a significant role in the regulation of suture fusion as well as in the maintenance of patency in the normal suture.

Authors+Show Affiliations

1Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University; and.1Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University; and.2Department of Neurosurgery, School of Medicine, Virginia Commonwealth University, Richmond, Virginia.2Department of Neurosurgery, School of Medicine, Virginia Commonwealth University, Richmond, Virginia.1Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University; and.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30215585

Citation

Cyprus, Garrett N., et al. "Spatial Regulation of Gene Expression in Nonsyndromic Sagittal Craniosynostosis." Journal of Neurosurgery. Pediatrics, vol. 22, no. 6, 2018, pp. 620-626.
Cyprus GN, Overlin JW, Vega RA, et al. Spatial regulation of gene expression in nonsyndromic sagittal craniosynostosis. J Neurosurg Pediatr. 2018;22(6):620-626.
Cyprus, G. N., Overlin, J. W., Vega, R. A., Ritter, A. M., & Olivares-Navarrete, R. (2018). Spatial regulation of gene expression in nonsyndromic sagittal craniosynostosis. Journal of Neurosurgery. Pediatrics, 22(6), pp. 620-626. doi:10.3171/2018.6.PEDS18229.
Cyprus GN, et al. Spatial Regulation of Gene Expression in Nonsyndromic Sagittal Craniosynostosis. J Neurosurg Pediatr. 2018 Dec 1;22(6):620-626. PubMed PMID: 30215585.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spatial regulation of gene expression in nonsyndromic sagittal craniosynostosis. AU - Cyprus,Garrett N, AU - Overlin,Jefferson W, AU - Vega,Rafael A, AU - Ritter,Ann M, AU - Olivares-Navarrete,René, PY - 2018/04/17/received PY - 2018/06/13/accepted PY - 2018/9/15/pubmed PY - 2019/7/10/medline PY - 2018/9/15/entrez KW - MSC = mesenchymal stem cell KW - TGF-β = transforming growth factor–β KW - TGF-β superfamily KW - Wnt signaling KW - craniofacial KW - craniosynostosis KW - micro-CT KW - qPCR = quantitative polymerase chain reaction SP - 620 EP - 626 JF - Journal of neurosurgery. Pediatrics JO - J Neurosurg Pediatr VL - 22 IS - 6 N2 - OBJECTIVECranial suture patterning and development are highly regulated processes that are not entirely understood. While studies have investigated the differential gene expression for different sutures, little is known about gene expression changes during suture fusion. The aim of this study was to examine gene expression in patent, fusing, and fused regions along sagittal suture specimens in nonsyndromic craniosynostosis patients.METHODSSagittal sutures were collected from 7 patients (average age 4.5 months) who underwent minimally invasive craniotomies at the Children's Hospital of Richmond at VCU under IRB approval. The sutures were analyzed using micro-CT to evaluate patency. The areas were classified as open, fusing, or fused and were harvested, and mRNA was isolated. Gene expression for bone-related proteins, osteogenic and angiogenic factors, transforming growth factor-β (TGF-β) superfamily, and Wnt signaling was analyzed using quantitative polymerase chain reaction and compared with normal sutures collected from fetal demise tissue (control).RESULTSMicro-CT demonstrated that there are variable areas of closure along the length of the sagittal suture. When comparing control samples to surgical samples, there was a significant difference in genes for Wnt signaling, TGF-β, angiogenic and osteogenic factors, bone remodeling, and nuclear rigidity in mRNA isolated from the fusing and fused areas of the sagittal suture compared with patent areas (p < 0.05).CONCLUSIONSIn nonsyndromic sagittal craniosynostosis, the affected suture has variable areas of being open, fusing, and fused. These specific areas have different mRNA expression. The results suggest that BMP-2, FGFR3, and several other signaling pathways play a significant role in the regulation of suture fusion as well as in the maintenance of patency in the normal suture. SN - 1933-0715 UR - https://www.unboundmedicine.com/medline/citation/30215585/Spatial_regulation_of_gene_expression_in_nonsyndromic_sagittal_craniosynostosis_ L2 - https://thejns.org/doi/10.3171/2018.6.PEDS18229 DB - PRIME DP - Unbound Medicine ER -