Dynamic Gene Expression in the Human Cerebral Cortex Distinguishes Children from Adults

Kirstin N Sterner,Morris Goodman,Lucie Grégoire,Amy M Boddy,Adi L Tarca,Lawrence I Grossman,Patrick R Hof,Harry T Chugani,Monica Uddin,Christopher W Kuzawa,Ryan L Raaum,Asad Abbas,Leonard Lipovich,Chet C Sherwood,Amy Weckle,Derek E Wildman

doi:10.1371/journal.pone.0037714

Abstract

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR≅0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development.

Highlights

Many of the behavioral traits that distinguish humans from other species are molded throughout development by an exceptional capacity to incorporate experience and learning into the production of culture [1]
We sought to identify which genes showed expression patterns in the cerebral cortex that are variable across individuals and to evaluate whether there were age differences in the degree of this variability
Among transcripts showing the greatest variance in expression levels, we found a significantly higher number of genes (n = 302) in which expression variability among individuals was greater in samples collected in children and young adolescence than those collected in adults

Summary

Introduction

Many of the behavioral traits that distinguish humans from other species are molded throughout development by an exceptional capacity to incorporate experience and learning into the production of culture [1]. This ability to learn results from changes that occur in the organization of the brain as the result of experiences. The cerebral cortex is continually remodeled in response to various molecular signals, as well as environmental stimuli [2] This phenotypic plasticity in the brain can occur at multiple levels, ranging from large-scale remapping of cortical areas to more subtle strengthening or weakening of synaptic connections [3]. Such changes in the regulation of gene expression may have significantly influenced human brain evolution [12]

Methods

Results

Conclusion