Role of Dach1 revealed using a novel inner ear-specific Dach1-knockdown mouse model.
Toru MiwaRyosei MinodaYoshihide IshikawaTomohito KajiiYorihisa OritaTakahiro OhyamaPublished in: Biology open (2019)
The Dach1 gene is expressed in the inner ear of normal mouse embryos in the area that differentiates into the cochlear stria vascularis (SV). We hypothesised that Dach1 downregulation in the inner ear would lead to SV dysplasia. However, because Dach1 knockout is embryonic lethal in mice, the role of Dach1 in the inner ear is unclear. Here, we established inner ear-specific Dach1-knockdown mice and showed that Dach1 downregulation 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-specific Dach1-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-specific Dach1-knockdown mice at embryonic stages. In summary, suppression of Dach1 expression 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.
Keyphrases
- epithelial mesenchymal transition
- induced apoptosis
- hearing loss
- signaling pathway
- cell cycle arrest
- single cell
- mouse model
- poor prognosis
- high fat diet induced
- type diabetes
- transforming growth factor
- cell therapy
- wild type
- oxidative stress
- endoplasmic reticulum stress
- insulin resistance
- long non coding rna
- genome wide identification
- drug induced