Twin-peak temporal regulation during human neocortical development

Understanding the temporal and spatial expression patterns of the human cerebral cortex is essential for expanding knowledge of its functionality. Previous analysis focused on the differentially expressed genes (DEGs) among cortical subregions revealed an hourglass model for interareal differences. However, the overall pattern of transcriptional differences during the development of every region remains to be fully explored. Here, analysing more than 800 neocortex samples from lifespan transcriptional profiles revealed that excitatory neurons are more regulated than inhibitory neurons in the foetal brain. Developmental DEGs tend to be resting state or memory encoding-related and are also involved in autism and Alzheimer's disease. In addition, twin peaks of DEGs occur during the development of each neocortex region, with a first peak appearing in the perinatal period and an unexpected second peak appearing around childhood. Genes in these peaks have similar functions, but the second peak is more inhibitory neuron related. All these results emphasize the significance of this unique temporal regulatory pattern for human neocortical development.