GSE123560 Schizophrenia-related microdeletion causes progressive brain ventricle enlargement through microRNA-dependent deceleration of motile cilia beating

Contributors : Tae-Yeon Eom ; Seung B Han ; Jieun Kim ; Jay Blundon ; Yong-Dong Wang ; Jing Yu ; Matthew Eicholtz ; Derek C Rose ; Kara Anderson ; Damian B Kaminski ; Stanislav S ZakharenkoSeries Type : Non-coding RNA profiling by arrayOrganism : Mus musculusProgressive ventricular enlargement is one of the most reproducible and recognizable structural abnormalities in schizophrenia, and is associated with more severe symptoms and poorer clinical outcome. The mechanisms of ventricular enlargement in schizophrenia is unknown. We identified that progressive ventricular enlargement is associated with deceleration of motile cilia beating in ependymal cells lining ventricular walls in murine models of schizophrenia-associated 22q11 deletion syndrome (22q11DS). The cilia beating deficit is caused by an aberrant elevation of Drd1, which is highly enriched in the motile cilia. Haploinsufficiency of the microRNA-processing gene Dgcr8 is responsible for the Drd1 elevation in ependymal cells of 22q11DS mice, and is mediated by reduction of Drd1-targeting microRNAs miR-674-3p and miR-382-3p. Replenishing miR-674-3p or miR-382-3p in 22q11DS mice rescued the motile cilia beating abnormalities and normalized the ventricular size. Knockdown of these microRNA mimicked cilia beating and ventricular deficits. Ventricular enlargement was also caused by Crispr/cas9-mediated deletion of the Drd1 seed site for miR-674-3p/miR-382-3p. This suggests that Dgcr8-miR-674-3p/miR-382-3p-Drd1 –depe...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by array Mus musculus Source Type: research