Identification of the Molecular Events Involved in the Development of Prefrontal Cortex Through the Analysis of RNA-Seq Data From BrainSpan

Abstract

Human brain development is a complex process that follows sequential orchestration of gene expression, begins at conceptual stages, and continues into adulthood. Altered profile of gene expression drives many cellular and molecular events required for development. Here, the molecular events during development of human prefrontal cortex (PFC) (as an important executive part of the brain) were investigated. First, the RNA-sequencing data of BrainSpan were used to obtain differentially expressed genes between each two developmental stages and then, the relevant biological processes and signaling pathways were deduced by gene set enrichment analysis. In addition, the changes in transcriptome landscape of PFC during development were analyzed and the potential biological processes underlie the changes were found. Comparison of the four regions of PFC based on their biological processes showed that additional to common biological processes and signaling pathways, each PFC region had its own molecular characteristics, conforming their previously reported functional roles in brain physiology. The most heterogeneity in transcriptome between the PFC regions was observed at the time of birth which was concurrent with the activity of some region-specific regulatory systems such as DNA methylation, transcription regulation, RNA splicing, and presence of different transcription factors and microRNAs. In conclusion, this study used bioinformatics to present a comprehensive molecular overview on PFC development which may explain the etiology of brain neuropsychiatric disorders originated from malfunctioning of PFC.