Role of Dach1 revealed using a novel inner ear-specific Dach1-knockdown mouse model

摘要

TheDach1gene is expressed in the inner ear of normal mouse embryos in the area that differentiates into the cochlear stria vascularis (SV). We hypothesised thatDach1downregulation in the inner ear would lead to SV dysplasia. However, becauseDach1knockout is embryonic lethal in mice, the role ofDach1in the inner ear is unclear. Here, we established inner ear-specificDach1-knockdown mice and showed thatDach1downregulation resulted in hearing loss, reduced endocochlear potential and secondary outer hair cell loss. There were no abnormalities in marginal cells and basal cells in the SV or spiral ligament in inner ear-specificDach1-knockdown mature mice. However, intermediate cell dysplasia and thinning of the SV were observed. Moreover, dynamic changes in the expression of key genes related to the epithelial-mesenchymal transition were observed in the lateral wall of the cochlear epithelium, which differentiated into the SV in inner ear-specificDach1-knockdown mice at embryonic stages. In summary, suppression ofDach1expression in the inner ear caused the epithelial-mesenchymal transition in the lateral wall of cochlear epithelium, resulting in loss of intermediate cells in the SV and SV dysplasia.This article has an associated First Person interview with the first author of the paper.