The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development.

Neuronal gene expression is tightly regulated in developing CNS. Here, we demonstrate the anti-neural function of phosphatase SCP1 (small C-terminal domain phosphatase 1) during development. We further show that the neuron-enriched microRNA miR-124 directly targets SCP1-3' untranslated region (UTR) to suppress SCP1 expression. In developing spinal cord, expression of miR-124 and SCP1 is complementary, and miR-124 antagonism phenocopies SCP1 overexpression and vice versa. In P19 cells, miR-124 suppresses SCP1 expression and induces neurogenesis, and SCP1 counteracts this proneural activity of miR-124. Our results suggest that, during CNS development, timely down-regulation of SCP1 is critical for inducing neurogenesis, and miR-124 contributes to this process at least in part by down-regulating SCP1 expression.