Temporal Specification and Bilaterality of Human Neocortical Topographic Gene Expression

The PFC, Broca area, and Wernicke area in humans display a temporarily enriched gene expression pattern distinct from mouse or macaque cerebrum at comparable prenatal stages.

“Thus, the PFC as well as the Broca and Wernicke association areas in humans, which are formed in the frontal and temporal lobes, display a temporarily enriched gene expression pattern that is distinct from the mice or macaque cerebrum at the comparable prenatal stages (e.g., [21, 22]).”

The basic structural and functional framework of the human brain is in place by the second year of life and perhaps earlier.

“These studies, along with more recent postmortem histological and gene-expression studies7, 8 (Box 1), suggest that the basic structural and functional framework of the human brain is in place by the second year of life and perhaps even earlier.”

Prenatal cortical development is characterized by robust regional differences in gene expression that are probably crucial for establishing area-specific subcortical-cortical and cortico-cortical projections.

“prenatal cortical development is characterized by robust regional differences in gene expression that are probably crucial for establishing area-specific subcortical-cortical and cortico-cortical projections8.”

Infancy and early childhood are characterized by relatively minimal differences in gene expression across cortical areas, as general neuronal and glial differentiation transcription programmes are initiated.

“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 initiated8.”

Fetal gene co-expression modules with prominent differential patterns among areas and gradient-like expression patterns also displayed divergence between humans and rhesus macaques, suggesting a possible role for differences in neocortical topographic patterns of gene expression in evolution of neural circuitry.

“Interestingly, the fetal gene co-expression modules that showed prominent differential patterns among areas and gradient-like expression patterns (Figure 5D–G), particularly during fetal development, also displayed divergence between humans and rhesus macaques (Figures 5H–K) (Pletikos et al., 2014), suggesting a possible role for differences in neocortical topographic patterns of gene expression”

Strong early and mid-fetal inter-areal transcriptional differences and gradients diminish during late fetal periods and postnatal development, especially infancy and childhood, and increase again after adolescence.

“These strong early and mid-fetal inter-areal transcriptional differences and gradients diminish during late fetal periods and postnatal development, especially during infancy and childhood, and increase again after adolescence (Figures 5B and C) (Pletikos et al., 2014).”

Primates share common, closely matched gene expression patterns in the neocortex, while the human frontal lobe is transcriptionally more complex.

“Comparison of the adult human and non-human primate brain transcriptomes shows that primates share common, closely matched gene expression patterns in the neocortex, while the human frontal lobe is transcriptionally more complex (Bernard et al., 2012; Konopka et al., 2012; Pletikos et al., 2014).”

Transcription profiles in the adult neocortex are relatively homogeneous throughout the cortex, although some heterogeneity exists.

“Surprisingly, it turned out that transcription profiles in the adult neocortex are relatively homogeneous throughout the cortex, although a certain level of heterogeneity still does exist (Hawrylycz et al., 2012; Kang et al., 2011; Pletikos et al., 2014)”