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Significance In the developing mammalian neocortex, neurons migrate a long distance from their birthplace to the positions where they form appropriate layers and networks, and dysregulation of this process has been implicated in brain malformation and neurological diseases. Given the fine correlation between temporal order of various sequentially generated neuronal cell types and their spatial distribution, migration speed needs to be tightly controlled to achieve correct neocortical layering, although the underlying mechanisms remain unclear. Here we show that the serine/threonine kinase Akt and its activator phosphoinositide-dependent protein kinase 1 (PDK1) regulate the speed of locomotion of mouse neocortical neurons through the cortical plate. Our data suggest that the PDK1–Akt axis regulates microtubule organization, in part by regulating the cytoplasmic dynein/dynactin complex, in migrating neurons.

PDK1–Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex