MicroRNA Targeting of CoREST Controls Polarization of Migrating Cortical Neurons

• MicroRNAs control radial migration through regulation of cortical neuron polarization
• miR-22 and miR-124 are critical regulators of neuron morphology during migration
• miR-22 and miR-124 target the CoREST/REST complex to fine-tune doublecortin expression

SummaryThe migration of cortical projection neurons is a multistep process characterized by dynamic cell shape remodeling. The molecular basis of these changes remains elusive, and the present work describes how microRNAs (miRNAs) control neuronal polarization during radial migration. We show that miR-22 and miR-124 are expressed in the cortical wall where they target components of the CoREST/REST transcriptional repressor complex, thereby regulating doublecortin transcription in migrating neurons. This molecular pathway underlies radial migration by promoting dynamic multipolar-bipolar cell conversion at early phases of migration, and later stabilization of cell polarity to support locomotion on radial glia fibers. Thus, our work emphasizes key roles of some miRNAs that control radial migration during cerebral corticogenesis.

Graphical AbstractFigure optionsDownload as PowerPoint slide