An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development

In human FMCD tissue, a small fraction of pS6+ neurons are enriched for somatic activating mutations of the PI3K-AKT-mTOR pathway. Sparse electroporation of the AKT3 mutation into the developing mouse brain causes a reelin-dependent, non–cell autonomous disruption of neuronal migration, leading to impaired cortical lamination and seizure-like epileptiform EEG activity.