Disabled-1-regulated adhesion of migrating neurons to radial glial fiber contributes to neuronal positioning during early corticogenesis

Disabled-1 regulates laminar organization in the developing mammalian brain. Although mutation of the disabled-1 gene in scrambler mice results in abnormalities in neuronal positioning, migratory behavior linked to Disabled-1 signaling is not completely understood. Here we show that newborn neurons in the scrambler cortex remain attached to the process of their parental radial glia during the entire course of radial migration, whereas wild-type neurons detach from the glial fiber in the later stage of migration. This abnormal neuronal-glial adhesion is highly linked to the positional abnormality of scrambler neurons and depends intrinsically on Disabled-1 Tyr220 and Tyr232, potential phosphorylation sites during corticogenesis. Importantly, phosphorylation at those sites regulates alpha3 integrin levels, which is critical for the timely detachment of migrating neurons from radial glia. Altogether, these results outline the molecular mechanism by which Disabled-1 signaling controls the adhesive property of neurons to radial glia, thereby maintaining proper neuronal positioning during corticogenesis.