MicroRNA-218 regulates neuronal radial migration and morphogenesis by targeting Satb2 in developing neocortex

Neuronal migration and morphogenesis are fundamental processes for cortical development. Their defects may cause abnormities in neural circuit formation and even neuropsychiatric disorders. Many proteins, especially layer-specific transcription factors and adhesion molecules, have been reported to regulate the processes. However, the involvement of non-coding RNAs in cortical development has not been extensively studied. Here, we identified microRNA-218 (miR-218) as a layer V-specific microRNA in mouse brains. Expression of miR-218 was elevated in patients with autism spectrum disorder (ASD) and schizophrenia. We found in this study that miR-218 overexpression in developing mouse cortex led to severe defects in radial migration, morphogenesis, and spatial distribution of the cortical neurons. Moreover, we identified Satb2, an upper-layer marker, as a molecular target repressed by miR-218. These results suggest an underlying mechanism of miR-218 involvement in neuropsychiatric disorders, and the interactions of layer-specific non-coding RNAs and proteins in regulating cortical development.(c) 2023 Elsevier Inc. All rights reserved.