Loss of miR-9-2 Causes Cerebral Hemorrhage and Hydrocephalus by Widespread Disruption of Cell-Type-Specific Neurodevelopmental Gene Networks

MIR-9-2 is a broadly and highly expressed microRNA in the developing brain and is frequently deleted in 5q14.3 Microdeletion Syndrome, a rare but severe neurodevelopmental disorder. Despite this, little attention has been paid to the unique contributions of MIR-9-2 to neurodevelopment and disease. We find that deletion of this microRNA leads to embryonic cerebral hemorrhages and severe hydrocephalus, while disrupting gene networks across a wide range of cell types in the developing brain, thus revealing underappreciated and non-redundant molecular, cellular, and system-wide functions for MIR-9-2 in neurodevelopment. Following E2A-Cre germline deletion of miR-9-2 in Mir9-2tm1Mtm transgenic mice, embryonic day (E)12.5 and E16.5 cerebral cortices were harvested from homozygous knock-out and wild-type littermate controls for snRNA-seq processing and analysis.