Genetic and Protein Expression Comparison of Tissues of Differing Embryonic Origin.

Abstract

Non-syndromic Craniosynostosis (CS) has an unknown etiology. The overproduction of thyroid hormones (THs) during pregnancy known as maternal hyperthyroidism has been cited by the CDC as a potential cause of CS. Elucidation of the mechanism for TH induced CS may allow for the creation of a novel more suitable treatment option. There are several signaling pathways involved in the differentiation and development of the tissues of the skull such as, BMP, Ihh, and Wnt. Wnt signaling has been linked to the differentiation of both embryonic mesoderm as well as neural crest cells, from which the relevant tissues of the skull originate. The goal of this study is to quantify and compare genetic and protein expression of relevant Wnt signaling molecules and their target genes within the Sagittal and Coronal sutures. Beta-Catenin is a Wnt signaling molecule that acts as a transcription factor modulating the expression of genes such as Runx2 and Twist1. These genes were selected as they are known to be involved in cranial development. Sutures were collected from an avian model of induced thyrotoxicosis and analyzed using qRT-PCR and western blotting. Results of the qRT-PCR showed a significant downregulation in Runx2 and Twist1 expression in the coronal sutures with no change in Twist1 and a significant upregulation of Runx2 expression in the sagittal sutures. Western blot results are still pending. While further investigation into these pathways is necessary, our findings conclude that these key pathways react differently to modulation by thyroid hormones in tissues of differing embryonic origin.