Precise regulation of neuronal migration termination is crucial for the establishment of brain cytoarchitectures. However, little is known how neurons terminate migration. We found that superficial layer cortical neurons (SLNs) migrate beyond their final destination and ectopically invade layer 1 in Plexin (Plxn) A2/A4 double-knockout mice as well as Semaphorin (Sema) 6A knockout mice. Cell-targeted gene expression and conditional knockouts indicated that Sema6A on radial glial cells and PlxnA2/A4 on SLNs are involved in this process. Given that Sema6A–PlxnA2/A4 trans-interactions generally induce a repulsive reaction, our results suggest that Sema6A–PlxnA2/A4 interaction elicits repulsion and weakens migrating neuron–substrate interactions, leading to migration termination.

Figure: Cortical neurons migrate toward the pial surface along radial glial cell fibers. Sema6A on radial glial cells and PlxnA2/A4 on migrating neurons are necessary for proper migration termination of superficial layer cortical neurons.