From trans to cis: transcriptional regulatory networks in neocortical development

Abstract

Transcriptional mechanisms mediated by the binding of transcription factors to cis-acting regulatory DNA elements play critical roles in directing gene expression. While transcription factors have been extensively studied, less effort has gone towards the identification and functional characterization of cis-regulatory elements and associated epigenetic modulation. However, due to methodological and analytical advances, more comprehensive studies of regulatory elements and mechanisms are now possible. Here we summarize recent progress in integrative analyses of these regulatory components in the development of the cerebral neocortex, the part of the brain involved in cognition and complex behavior. These studies are uncovering not only the underlying transcriptional regulatory networks, but also how these networks are altered across species and in neurological and psychiatric disorders.

Role of ortho‐retronasal olfaction in mammalian cortical evolution

“…How does this hypothesis relate to current studies of the neurogenesis of cortical neuron types (Molnár et al, 2014; Shibata et al, 2015)? In all vertebrates, epithelium in the ventricular zone (VZ) is the primary embryonic neurogenic source, and in mammals the major source of cells in the deeper neocortical layers (5–6).…”

Genetics and mechanisms leading to human cortical malformations

“…Furthermore, differentially expressed genes within the developing human brain may have an elevated substitution rate in humans and in other species, particularly in conserved non-coding sequences (CNSs) [321], which may also help explain some human disorders. Human-specific non-coding regions of DNA, including human-accelerated CNSs (HACNSs), have also been shown to play important roles in human brain development by regulating genes having key roles in temporal and spatial dynamics compared to the mouse [322,323]. These differences need to be further studied to have the best chance of understanding human conditions.…”

Imaging structural and functional brain development in early childhood

“…By contrast, infancy and early childhood are characterized by relatively minimal differences in gene expression across cortical areas, as more ‘general’ neuronal and glial differentiation transcription programmes are initiated 8 . These developmental programmes are mediated by transcription factors that bind to specific genomic sequences (such as cis -regulatory elements), as well as transcriptional cofactors, chromatin regulators, epigenetic modifications, RNA-binding proteins and non-coding RNAs 157 . Genomic variants that influence these processes are expected to have an important role in generating individual differences in brain structure and function.…”