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Spatiotemporal dynamics of the postnatal developing primate brain transcriptome.

  • Author(s): Bakken, Trygve E
  • Miller, Jeremy A
  • Luo, Rui
  • Bernard, Amy
  • Bennett, Jeffrey L
  • Lee, Chang-Kyu
  • Bertagnolli, Darren
  • Parikshak, Neelroop N
  • Smith, Kimberly A
  • Sunkin, Susan M
  • Amaral, David G
  • Geschwind, Daniel H
  • Lein, Ed S
  • et al.
Abstract

Developmental changes in the temporal and spatial regulation of gene expression drive the emergence of normal mature brain function, while disruptions in these processes underlie many neurodevelopmental abnormalities. To solidify our foundational knowledge of such changes in a primate brain with an extended period of postnatal maturation like in human, we investigated the whole-genome transcriptional profiles of rhesus monkey brains from birth to adulthood. We found that gene expression dynamics are largest from birth through infancy, after which gene expression profiles transition to a relatively stable state by young adulthood. Biological pathway enrichment analysis revealed that genes more highly expressed at birth are associated with cell adhesion and neuron differentiation, while genes more highly expressed in juveniles and adults are associated with cell death. Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex. Using network analysis, we identified 27 co-expression modules containing genes with highly correlated expression patterns that are associated with specific brain regions, ages or both. In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes. This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD.

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