Identification of potential molecular mechanism related to craniofacial dysmorphism caused by FOXI3 deficiency

Abstract Background Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 ( FOXI3 ) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now. Method In this study, we first constructed a Foxi3 deficiency ( Foxi3 −/− ) mouse model to verify the craniofacial phenotype of Foxi3 −/− mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real‐time PCR. Results By observing the phenotype of Foxi3 −/− mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K‐Akt signaling pathway. Quantitative real‐time PCR results showed that the expression of PI3K‐Akt signaling pathway‐related gene Akt2 was significantly increased in Foxi3 −/− mice. Conclusion The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K‐Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction.