title: Genomic divergence and brain evolution: How regulatory DNA influences development of the cerebral cortex.
abstract: The cerebral cortex controls our most distinguishing higher cognitive functions. Human-specific gene expression differences are abundant in the cerebral cortex, yet we have only begun to understand how these variations impact brain function. This review discusses the current evidence linking non-coding regulatory DNA changes, including enhancers, with neocortical evolution. Functional interrogation using animal models reveals converging roles for our genome in key aspects of cortical development including progenitor cell cycle and neuronal signaling. New technologies, including iPS cells and organoids, offer potential alternatives to modeling evolutionary modifications in a relevant species context. Several diseases rooted in the cerebral cortex uniquely manifest in humans compared to other primates, thus highlighting the importance of understanding human brain differences. Future studies of regulatory loci, including those implicated in disease, will collectively help elucidate key cellular and genetic mechanisms underlying our distinguishing cognitive traits.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.|Department of Cell Biology, Duke University Medical Center, Durham, NC, USA.|Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.|Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Silver
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002540:Cerebral Cortex / Q000254:growth & development*; D004247:DNA / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D023281:Genomics / Q000379:methods; D006801:Humans; D038081:Organogenesis / Q000235:genetics*
chemical_list: D004247:DNA
keywords: corticogenesis; enhancer; evolution; neocortex; stem cell