Transcriptional Architecture of the Primate Neocortex

Abstract

SUMMARY Genome-wide transcriptional profiling was used to characterize the molecular underpinnings of neocortical organization in rhesus macaque, including cortical areal specialization and laminar cell type diversity. Microarray analysis of individual cortical layers across sensorimotor and association cortices identified robust and specific molecular signatures for individual cortical layers and areas, prominently involving genes associated with specialized neuronal function. Overall, transcriptome-based relationships were related to spatial proximity, being strongest between neighboring cortical areas and between proximal layers. Primary visual cortex (V1) displayed the most distinctive gene expression compared to other cortical regions in rhesus and human, both in the specialized layer 4 as well as other layers. Laminar patterns were more similar between macaque and human compared to mouse, as was the unique V1 profile that was not observed in mouse. These data provide a unique resource detailing neocortical transcription patterns in a non-human primate with great similarity in gene expression to human.

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

“…However, in adult macaque monkeys, a number of genes with maximal variation in expression across cortical areas are expressed in rostrocaudal gradients. This finding may reflect persistent traces of gradients in developmental origin and timing during cortical neurogenesis (8).…”

“…Graded expression along a principal axis is common in the adult cerebral cortex and often takes the form of rostrocaudal molecular gradients (8). To assess whether physical distance accounted for transcriptional similarity, the MNI atlas coordinates of brain samples were sorted along the rostrocaudal axis for two representative individuals (Fig.…”

“…Gradients in the expression of key transcription factors are strong drivers of cortical arealization and patterning during development (51)(52)(53). In adults, gene expression is fairly uniform across cortical regions (8,18,34). However, in adult macaque monkeys, a number of genes with maximal variation in expression across cortical areas are expressed in rostrocaudal gradients.…”

“…Previous work examining transcriptional variation in nonhuman primates and rodents indicate that molecular similarities between cortical regions in the adult brain are best explained by spatial proximity (7,8). Molecular variation often takes the form of graded expression along a principal axis, in many cases appearing as rostrocaudal gradients across the cortex (8).…”

“…Previous work examining transcriptional variation in nonhuman primates and rodents indicate that molecular similarities between cortical regions in the adult brain are best explained by spatial proximity (7,8). Molecular variation often takes the form of graded expression along a principal axis, in many cases appearing as rostrocaudal gradients across the cortex (8). The strong tendency for transcriptional variation to follow spatial proximity in the adult cortex likely reflects both functional gradients, as well as their developmental origins in terms of physical and temporal adjacency during neurogenesis of cells destined for neighboring locations in the cortex (at least for cells derived from the ventricular proliferative pool) (7).…”