Transcriptional Profiling of the Developing Rat Brain Reveals That the Most Dramatic Regional Differentiation in Gene Expression Occurs Postpartum

Abstract

Neural development involves the expression of ensembles of regulatory genes that control the coordinate and region-specific expression of a host of other genes, resulting in the unique structure, connectivity, and function of each brain region. Although the role of some specific genes in neural development has been studied in detail, we have no global view of the orchestration of spatial and temporal aspects of gene expression across multiple regions of the developing brain. To this end, we used transcriptional profiling to examine expression levels of 9955 genes in the hypothalamus, hippocampus, and frontal cortex across seven stages of postnatal development and up to four stages of prenatal development in individual male rats (six per group). The results reveal dramatic changes across development in >97% of the neurally expressed genes. They also uncover a surprising degree of regional differentiation occurring after birth and through the first 2 weeks of life. Cluster analysis identifies 20 clusters of transcripts enriched in genes related to particular functions, such as DNA metabolism, nuclear function, synaptic vesicle transport, myelination, and neuropeptide hormone activity. Thus, groups of genes with related functions change in the brain at specific times, possibly marking critical periods for each function. These findings can broadly serve as a backdrop for studying the role of individual genes in neural development. They also underscore the importance of early postnatal life in the rat, which corresponds to late gestation in the human, as a critical late phase of neural organization and differentiation, even in subcortical regions.