Microarray analysis of the role of regional dura mater in cranial suture fate.
BACKGROUND
Craniosynostosis, the premature fusion of cranial sutures, results in serious neurologic and morphologic abnormalities when left untreated. Surgical excision of the fused sutures and remodeling of the skull remains the standard therapy. Development of novel, minimally invasive therapies for craniosynostosis will undoubtedly be dependent on a more thorough understanding of the molecular mechanisms underlying this abnormality. Significant evidence suggests the influence of regional dura mater on the behavior of the overlying suture complex. The mouse model has been instrumental in investigating this observation because of the natural juxtaposition of the posterior frontal suture, which fuses early in life, with the other cranial sutures, which remain patent.


METHODS
The authors used microarray analysis to compare genomic changes in the dura mater underlying the posterior frontal and sagittal sutures of mice. Suture-associated dura mater was harvested from mice before (postnatal day 5), during (postnatal day 10), and after (postnatal day 20) posterior frontal suture fusion (n = 20 mice for each of the three time points).


RESULTS
Microarray results confirmed differential regulation of genes involved in paracrine signaling, extracellular matrix, and bone remodeling between the dura mater underlying the fusing posterior frontal suture and the patent sagittal suture.


CONCLUSIONS
These data confirm global differences in gene expression between regional dura mater underlying fusing and patent sutures. These results provide further insight into potential molecular mechanisms that may play a role in cranial suture biology.
Kwan
Matthew D
MD
Stanford, Calif. From the Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, and the Department of Surgery, Stanford University School of Medicine.
Wan
Derrick C
DC
Wang
Zhen
Z
Gupta
Deepak M
DM
Slater
Bethany J
BJ
Longaker
Michael T
MT
D000135:Acid Phosphatase / Q000235:genetics; D000367:Age Factors; D000818:Animals; D016723:Bone Remodeling / Q000235:genetics*; D003393:Cranial Sutures / Q000378:metabolism*; D004388:Dura Mater / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D060850:LIM-Homeodomain Proteins; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication / Q000235:genetics; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D000071681:Tartrate-Resistant Acid Phosphatase; D014157:Transcription Factors / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D053781:Transforming Growth Factor beta2 / Q000235:genetics; D053782:Transforming Growth Factor beta3 / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics
C491382:Fhl2 protein, mouse; D018398:Homeodomain Proteins; C513121:IGF2 protein, mouse; D007527:Isoenzymes; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; C508961:Tgfb1 protein, mouse; C509042:Tgfb2 protein, mouse; C509045:Tgfb3 protein, mouse; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse; D007335:Insulin-Like Growth Factor II; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse