Role of miR-146a in mouse brain development: relevance for developmental brain disorders

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally. miRs are involved in a wide range of regulation networks, including those involved in brain development. We and other showed an upregulation of miR-146a in autism spectrum disorders, intellectual disability and epilepsy. Taking advantage of a mouse model constitutively inactivated for miR-146a, we investigated its functions during brain development using a combination of imaging, molecular, cell biology techniques and behavioral studies. We demonstrated that loss of miR-146a causes time and region specific expression defects in the mouse brain. Pyramidal and interneurons are the most severely affected cell types with deregulated pathways reflecting different stages of neuronal differentiation and synaptic maturation. We showed that absence of miR-146a impairs the balance between proliferation and differentiation of neural progenitors. We observed no difference in neither brain weight nor total volume but an increased hemispheric asymmetry of hippocampal volume. Lastly, impaired associative memory was also observed. Our results show that miR-146 is important for proper brain development and support the hypothesis that miR-146a deregulation may play a role in developmental brain disorders. We tested the neocortex at E14.5. For P30 and P6 stages, we tested the amygdala, hippocampus and sensoricortex. Each region was sampled at least 3 times (per genotype) from mice born to different moms.