In summary, the results reported in this study show that IGF-1R is necessary for the early orientation and polarity switch of cortical plate neurons and, therefore, for normal neuron migration and differentiation, including axonal outgrowth and the establishment of neuronal polarity. Finally, we propose that the PI3K pathway could be involved in IGF-1R effects on cortex formation. More investigation will be needed in order to identify all the components of the IGF-1R/PI3K pathway implicated in the regulation of these phenomena.