Untangling Cortical Complexity During Development

The cerebral cortex is composed of billions of morphologically and functionally distinct neurons. These neurons are produced and organized in a regimental fashion during development. The ability of neurons to encode and elicit complex cognitive and motor functions depends on their precise molecular processes, identity, and connectivity established during development. Elucidating the cellular and molecular mechanisms that regulate development of the neocortex has been a challenge for many years. The cerebral cortical neuronal subtypes are classified based on morphology, function, intrinsic synaptic properties, location, connectivity, and marker gene expression. Development of the neocortex requires an orchestration of a series of processes including the appropriate determination, migration and positioning of the neurons, acquisition of layer-specific transcriptional hallmarks, and formation of precise axonal projections and networks. Historically, fate mapping, genome-wide analysis, and transcriptome profiling have provided many opportunities for the characterization of neuronal subtypes. During the course of this review, we will address the regimental organization of the cerebral cortex, dissect the cellular subtypes that contribute to cortical complexity, and outline their molecular hallmarks to understand cellular diversity in the cerebral cortex with a focus on the excitatory neurons.