Lineage origins of GABAergic versus glutamatergic neurons in the neocortex

•Fate-restricted progenitors in the pallium produce subtypes of excitatory projection neurons.•Fate-restricted progenitors in the subpallium generate subtypes of interneurons.•Pallium and subpallium may contain subsets of multipotent cortical progenitors.•Radial units contain neurons that are generated from diverse and spatially segregated progenitors.

Neocortical circuits are assembled from subtypes of glutamatergic excitatory and GABAergic inhibitory neurons with divergent anatomical and molecular signatures and unique physiological properties. Excitatory neurons derive from progenitors in the pallium, whereas inhibitory neurons originate from progenitors in the subpallium. Both classes of neurons subsequently migrate along well-defined routes to their final target area, where they integrate into common neuronal circuits. Recent findings show that neuronal diversity within the lineages of excitatory and inhibitory neurons is in part already established at the level of progenitor cells before migration. This poses challenges for our understanding of how radial units of interconnected excitatory and inhibitory neurons are assembled from progenitors that are spatially segregated and diverse in nature.