Cerebral cortex assembly: generating and reprogramming projection neuron diversity

•The cerebral cortex contains many subtypes of excitatory and inhibitory neurons.•Excitatory (projection) neurons (PNs) send axons to targets within and outside the cortex.•Several mechanisms are responsible for generating PN diversity.•Mature PNs retain the ability to reprogram class-specific features in vivo.•In vivo reprogramming of PN identity could represent a novel substrate for plasticity.

The mammalian cerebral cortex is responsible for the highest levels of associative, cognitive and motor functions. In the central nervous system (CNS) the cortex stands as a prime example of extreme neuronal diversity, broadly classified into excitatory projection neurons (PNs) and inhibitory interneurons (INs). We review here recent progress made in understanding the strategies and mechanisms that shape PN diversity during embryogenesis, and discuss how PN classes may be maintained, postnatally, for the life of the organism. In addition, we consider the intriguing possibility that PNs may be amenable to directed reprogramming of their class-specific features to allow enhanced cortical plasticity in the adult.