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.
Keywords: Cortical development; Layer-specific gene; MicroRNA-218; Morphogenesis; Radial migration; Satb2.
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