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 (AC-KI mice). The phos-phorylation of cofilin, an actin-depolymerizing protein, was remarkably decreased in the hippocampus of the AC-KI mice. Exogenous expression of pseudo-phosphorylated cofilin rescued the ectopic positioning of neurons in the hippocampus of AC-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.

Automated summary

Reelin, a secreted glycoprotein, is important for neuronal migration during brain development. This study found that the deletion of Reelin's C-terminal region (CTR) impaired the migration of late-born neurons in the hippocampus. It was also discovered that the phosphorylation of cofilin, an actin-depolymerizing protein, was reduced in the hippocampus of mice with deleted Reelin CTR. Exogenous expression of pseudo-phosphorylated cofilin rescued the abnormal positioning of neurons in the hippocampus. These findings suggest that Reelin CTR is necessary for the migration of late-born neurons in the hippocampus and involves the phosphorylation of cofilin.