The real role of reelin

Attractants and repellents shunt neurons into their correct final location. But now Iris Hack, Harold Cremer (Université Mediterranée, Marseille, France), and colleagues have found evidence that reelin fits into neither of these categories. They propose, instead, that reelin converts cells that are migrating in association with each other into individual cells that can strike out alone to find their final position.

This conclusion comes over fifty years after the locomoter abnormality of reeler mice was first described. Loss of reelin, the product of the reeler gene, causes a failure of older neurons to migrate through the layers of younger neurons in the cortex. But, says Cremer, “the available data gave no clear idea of what reelin was doing.”

Cremer studied not the cortex but the adult olfactory bulb, where he found that reelin was required for the ongoing arrival of new interneurons. Without reelin, incoming chains of migrating interneurons piled up at the entrance to the olfactory bulb, and failed to undergo their individual migrations to their final positions.

In in vitro assays, the group showed that reelin was neither a repellent nor attractant but acted to dissociate the interneurons from each other. In both the olfactory bulb and the cortex, this dissociation appears to be necessary for the final migration step. (The dissociation in the cortex displaces migrating neurons from the glial cells that are acting as their guides.) The direction of postdissociation migration is probably driven by cues other than reelin. ▪

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