Abstract
Precise regulation of migration termination is crucial for the establishment of cortical laminar structure. However, little is known about how neurons terminate migration. Here we analyzed the role of Plexin A2 and A4 (PlxnA2/A4) receptors and Semaphorin 6A (Sema6A) ligand on this process, focusing on an interaction between migrating neurons and their substrates. In PlxnA2/A4 double-knockout as well as Sema6A mutant mice, a superficial layer neurons subset ectopically invades layer I. This abnormality manifests at a time when these neurons arrive at their destinations. PlxnA2/A4 proteins are abundant on their leading processes, while Sema6A mRNA is enriched in somata of radial glial cells. Cell-targeted gene expression and conditional knockouts confirm that these molecules are required in their respective cells. Collectively, these results suggest that the well-timed appearance of the repulsive signaling mediated by Sema6A-PlxnA2/A4 weakens the interaction between migrating neurons and radial glial cells, which leads to migration termination.
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