Neuronal miR-17-5p contributes to interhemispheric cortical connectivity defects induced by prenatal alcohol exposure

Structural and functional deficits in brain connectivity have been reported in patients with fetal alcohol spectrum disorders (FASD); however, whether and how prenatal alcohol exposure (PAE) affects the axonal development of neurons and disrupts wiring between brain regions is unknown. We developed a mouse model of moderate alcohol exposure during prenatal brain wiring to study the impact of PAE on corpus callosum (CC) development. PAE induced aberrant navigation of interhemispheric CC axons that persisted even after the end of the exposure, causing ectopic termination in the contralateral cortex. We identified neuronal miR-17-5p and its target ephrin type A receptor 4 as mediators of the effect of alcohol on contralateral targeting of CC axons. Alteration of microRNA-mediated regulation of axon guidance signaling by prenatal alcohol exposure may affect interhemispheric cortical connectivity and the associated behavior in FASD. Overall design: Comparative gene expression profiling analysis of RNA-seq data of P0 cortical neurons electroporated with control plasmid (Cont) or miR-17-5P sponge (spg17)