Differential gene and transcript expression in murine right and left maxillo-mandibular complex

Facial asymmetry, seen in routine orthodontic patients as well as in patients with congenital defects like craniofacial microsomia, is not well understood. This study investigates differential gene and transcript expression between murine right and left maxillo-mandibular (MxMn) complexes at embryonic (E) day 14.5.

We harvested three wild-type mice embryos and carefully hemi-sectioned MxMn complexes into right and left halves. We confirmed equal expression of house-keeping genes, by RT-PCR, in right and left MxMn complexes. We isolated total RNA using Qiazol mRNAeasy kit and performed paired-end whole mRNA sequencing at LC Sciences (Houston, TX). Differential gene/transcript analyses (>1 log-fold change; p<0.05; q<0.1) were performed. Mouse Genome Informatics (MGI) database and gnomAD constraint scores were used to prioritize differentially expressed genes/transcripts.

In the right MxMn complex (comparison to left), there were 842 upregulated/520 downregulated transcripts and 1079 upregulated/79 downregulated genes. Of these, 46 upregulated/40 downregulated transcripts and 47 upregulated/6 downregulated genes were reported to be associated with craniofacial phenotypes in the MGI database. Several human conditions with craniofacial phenotypes were also associated with these genes/transcripts. Additionally, several of the differentially expressed genes/transcripts associated with craniofacial phenotype in MGI database also had gnomAD constraint loss-of-function scores less than 0.6; this suggests that these differentially expressed genes/transcripts are critical in the ontogeny of human development.

These findings indicate that there is significant differential expression of genes/transcripts between E14.5 murine right and left MxMn complexes. When these findings are extrapolated to humans, it may provide a biological basis to understand facial asymmetry. Further experiments are required to validate these findings.