Cunningham, Michael LHomayounfar, Negar2014-02-242015-12-142014-02-242013Homayounfar_washington_0250O_12596.pdfhttp://hdl.handle.net/1773/25036Thesis (Master's)--University of Washington, 2013The human calvaria has five major sutures (the metopic, coronal, sagittal, squamosal and lambdoid). These sutures consist of intrasutural mesenchyme (ISM) each flanked by two bones. The presence of unossified sutures facilitates fetal movement through the birth canal, as well as a growth center, allowing for brain growth. During growth of the calvaria, osteogenesis takes place at ectocranial and endocranial surfaces and the osteogenic front, the leading edge of each bone. The premature fusion of the sutures is called craniosynostosis. Although there are hundreds of studies investigating the molecular causes of craniosynostosis, the molecular mechanisms involved in the normal physiological development of each suture are not well understood. To study the mechanisms involved in normal development one must consider that sutures may be biologically distinct from each other. Known differences include the prevalence of being involved in synostosis, the type of mutations causing premature fusion of each suture, the timing of physiologic fusion and their embryonic origins. These differences suggest the existence of distinct molecular mechanisms controlling the development of each suture. Although previous investigations suggest that different embryonic origins of the compartments of suture complexes (ISM and two flanking bones) may account for these differences, there have not been adequate studies on human calvaria to resolve this issue. In this study, we obtained samples from human fetal calvaria. We investigated global gene expression of cells from the frontal and parietal bones and the metopic and sagittal ISM in order to assess the presence of an expression signature related to their embryonic origins. Furthermore, using a co-culture technique we evaluated changes in the gene expression, proliferation and differentiation of cells from different cranial compartments. This work has revealed that among the four compartments, the frontal and parietal bones have the most distinct gene expression profiles despite being of the same tissue type. We found correlated expression of two groups of genes which separate frontal/metopic compartments from parietal/sagittal compartments. Several of these genes have important roles in neural crest development. We will present data that suggest a signature of embryonic origin still exists in calvarial compartments early in the second trimester of human development. Gene expression profiling of these compartments suggests frontal/metopic versus parietal/sagittal compartments have distinct profiles related to proliferation, differentiation and extracellular matrix (ECM) production.application/pdfen-USCopyright is held by the individual authors.cranial suture; embryonic origin; gene expression; suture fusionCellular biologyMolecular biologyDevelopmental biologydentistryThesis