The Mechanism of MSX1 and PAX9 Implication in Tooth Development Based on the Weighted Gene Co-Expression Network Analysis

In this study, we investigated the mechanism by which Msx1 and Pax9 affect tooth development in mice. The microarray data GSE32321, which contains Msx1 and Pax9 wildtype and knockout samples from mice oral epithelium (Epi) and dental mesenchymal (Mes) cells, was used to identify the differentially expressed genes (DEGs). The highest associated gene modules were then explored in the Epi-Msx, Epi-Pax, Mes-Msx, and Mes-Pax groups by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) database analysis and hub gene screening were performed on the modules with the highest relevance. A total of 1467, 986, 1212, and 1293 DEGs were identified in the Epi-Msx, Epi-Pax, Mes-Msx, and Mes-Pax groups, respectively. Four highest associated gene modules were identified. GO enrichment analysis showed that the negative regulation of cell proliferation, cell adhesion, blood vessel development, and blood vessel morphogenesis was involved in tooth development. We further identified the hub genes IDH3A , SSPN , F13A1, and CBLN1 , and found that gene expression values varied at different time points during tooth development. Moreover, IDH3A and CBLN1 were shown to be involved in oxidoreduction coenzyme metabolic processes and cell-cell adhesion. Overall, Msx1 and Pax9 play an important role in tooth development in mice, an effect which is probably associated with their regulation of IDH3A , SSPN , F13A1, and CBLN1.