Abstract
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.
Highlights
The human cerebral neocortex is formed through development and involved in various complex behaviours
To characterize the global transcriptional regulation pattern per neocortex subregion, we collected 886 samples of brain regional expression data from the Human Brain Transcriptome (HBT) database[10], which spans from 10 weeks post conception to 82 years of age
Our results show that 11,771 genes were differentially expressed between any two developmental stages in at least one neocortical region (Supplementary Table S1), which accounted for 85% of all 13,834 expressed genes, suggesting that these neocortex regions are heavily regulated during brain development
Summary
The human cerebral neocortex is formed through development and involved in various complex behaviours. Understanding the development patterns of human brain regions at the molecular level is of vital importance as it may provide a more comprehensive view of the uniqueness of the human brain[1,2,3,4,5]. Due to advancements in microarray and next-generation sequencing technology, most transcriptional activities of mRNAs can be accessed in different brain regions at relatively low cost. These technologies revealed that 86% of genes are expressed in the primate brain, and ~82% of genes are expressed in the cerebral neocortex[6,7,8,9,10]. Examining the transcriptional activities in multiple brain regions across the lifespan has demonstrated that among 11 cortex regions, an hourglass model was proposed, which indicates that the transcriptional divergence among different subcortical regions is more significant in early and late periods of development than in childhood[11]
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