Reelin regulates the migration of late-born hippocampal CA1 neurons via cofilin phosphorylation

Reelin, a large secreted glycoprotein, plays an important role in neuronal migration during brain development. The C-terminal region (CTR) of Reelin is involved in the efficient activation of downstream signaling and its loss leads to abnormal hippocampal layer formation. However, the molecular mechanism by which Reelin CTR regulates hippocampal development remains unknown. Here, we showed that the migration of late-born, but not early-born, neurons is impaired in the knock-in mice in which Reelin CTR is deleted (ΔC-KI mice). The phosphorylation of cofilin, an actin-depolymerizing protein, was remarkably decreased in the hippocampus of the ΔC-KI mice. Exogenous expression of pseudo-phosphorylated cofilin rescued the ectopic positioning of neurons in the hippocampus of ΔC-KI mice. These results suggest that Reelin CTR is required for the migration of late-born neurons in the hippocampus and that this event involves appropriate phosphorylation of cofilin. •The hippocampal CA1 layer splits in mice lacking Reelin C-terminal (ΔC-KI).•The migration of late-born, but not early-born, neurons is impaired in ΔC-KI mice.•Phosphorylation of cofilin is decreased in the hippocampus of ΔC-KI mice.•Exogenous expression of pseudo-phosphorylated cofilin rescues the migration defects.