The Determination of the Effects of Msx2 Expression on Cell Growth and Apoptotsis in Vivo
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Proper skull development is dependent upon complex epithelial-mesenchymal interactions between the developing flat bones of the calvaria and the underlying dura mater. Craniosynostosis, a common human birth defect, occurs when calvarial sutures prematurely fuse, causing abnormal skull development. Craniosynostosis occurs in one out of every thousand babies born, with both genetic and environmental causes. This birth defect is known to be a very significant biomedical burden, seeing that the only way to cure severe craniosynsostosis is by surgical separation of the fused calvarial bones. Studies have shown that a mutation in the homeodomain of MSX2 is associated with Boston type craniosynostosis. This mutation causes a substitution of the amino acid Proline with Histidine in position 7 of the MSX2 homeobox. It was hypothesized that the mechanism by which MSX2 misregulation leads to craniosynostosis in humans and mice may be related to preprogramlned cell death or apoptosis. This was tested by creating a murine model of the human birth defect, by misregulatation of the wildtype or Pr07His mutant Msx2 in transgenic mice. Both transgenic and nontransgenic mice from the same litter were tested for the presence of apoptosis in the calvarial sutures with the Oncor Apop Tag in situ apoptosis kit at various developmental stages. Preliminary data showed reduced cell growth and increased apoptosis in cell populations of the sagittal suture, of misregulated Msx2 tissues, concluding that apoptosis may be the likely mechanism by which misregulated Msx2 leads to craniosynostosis.