A balancing Akt: How to fine-tune neuronal migration speed

Abstract

In the developing mammalian neocortex, newborn neurons produced deep in the brain from neural stem/progenitor cells set out for a long journey to reach their final destination at the brain surface. This process called radial neuronal migration is prerequisite for the formation of appropriate layers and networks in the cortex, and its dysregulation has been implicated in cortical malformation and neurological diseases. Considering a fine correlation between temporal order of cortical neuronal cell types and their spatial distribution, migration speed needs to be tightly controlled to achieve correct neocortical layering, although the underlying molecular mechanisms remain not fully understood. Recently, we discovered that the kinase Akt and its activator PDK1 regulate the migration speed of mouse neocortical neurons through the cortical plate. We further found that the PDK1-Akt pathway controls coordinated movement of the nucleus and the centrosome during migration. Our data also suggested that control of neuronal migration by the PDK1-Akt pathway is mediated at the level of microtubules, possibly through regulation of the cytoplasmic dynein/ dynactin complex. Our findings thus identified a signaling pathway controlling neuronal migration speed as well as a novel link between Akt signaling and cytoplasmic dynein/dynactin complex.