Unknown,Transcriptomics,Genomics,Proteomics

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Functional annotation of genes differentially expressed between primary motor and prefrontal association cortices of macaque brain

ABSTRACT: DNA microarray-based genome-wide transcriptional profiling and gene network analyses were used to characterize the molecular underpinnings of the frontal neocortical organization in rhesus macaque, with particular focus on the differences in the functional annotation of genes in the primary motor cortex and the prefrontal association cortex. Biofunctional analysis of the differentially expressed genes showed that the list of genes selectively expressed in the primary motor cortex were enriched with genes involved in development, oligodendrocyte function, and increased energy consumption, whereas the list of genes selectively expressed in the prefrontal association cortex were enriched with genes involved in cell morphology and calcium dynamics. These functional differences in selectively expressed genes may reflect the fundamental molecular structure of each cortex. Brain tissue was obtained from 4 adolescent rhesus monkeys (Macaca mulatta) aged between 2.6 and 2.7 years that had been bred in group cages without being subjected to any experimental treatment. Adequate measures were taken to minimize pain and discomfort, in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80M-bM-^@M-^S23). The monkeys were perfused with 500M-bM-^@M-^S1000 ml of ice-cold saline containing heparin sodium (1000 U/ml, Novo Heparin; Leo Pharmaceutical Products, Ballerup, Denmark) through the ascending aorta within 15 min of an overdose injection of pentobarbital sodium (50 mg/kg, i.p., Somnopentyl; Kyoritsu Shoji, Tokyo, Japan). The 2 neocortical areas (M1 and A46) were identified by sulcal landmarks. We used the forelimb region of M1 for the present analysis, which is located around the superior genu of the central sulcus. A46 was obtained from both the upper and lower banks of the principal sulcus. Each area from the left hemispheres was dissected on crushed ice and immediately frozen in liquid nitrogen.

ORGANISM(S): Macaca mulatta

SUBMITTER: Toshio Kojima

PROVIDER: E-GEOD-37997 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Genome-wide transcriptional profiling allows characterization of the molecular underpinnings of neocortical organization, including cortical areal specialization, laminar cell type diversity and functional anatomy. Microarray analysis of individual cortical layers across sensorimotor and association cortices in rhesus macaque demonstrated robust and specific laminar and areal molecular signatures driven by differential expression of genes associated with specialized neuronal function. Gene expression corresponding with laminar architecture was generally similar across cortical areas, although genes with robust areal patterning were often highly laminar as well, and these patterns were more highly conserved between macaque and human as compared to mouse. Layer 4 of primate primary visual cortex displayed a distinct molecular signature compared to other cortical regions, a specialization not observed in mouse. Overall, transcriptome-based relationships were strongest between proximal layers in a cortical area, and between neighboring areas along the rostrocaudal axis, reflecting in vivo cortical spatial topography and therefore a developmental imprint. Tissue from male and female monkeys (n = 2-3 animals/gender) was collected from anterior cingulate gyrus (ACG), layers 2, 3, 5, 6; orbitofrontal cortex (OFC), layers 2, 3, 5, 6; dorsolateral prefrontal cortex (DLPFC), layers 2-6; primary motor cortex (M1), layers 2, 3, 5, 6; primary somatosensory cortex (S1), layers 2-6; primary auditory cortex (A1), layers 2-6; primary visual cortex (V1), layers 2-6 including 4A, 4B, 4Calpha (4Ca), 4Cbeta (4Cb); secondary visual cortex (V2), layers 2-6; middle temporal area (MT), layers 2-6; temporal area (TE), layers 2-6; hippocampus, CA1, CA2, CA3, dentate gyrus (DG); and dorsal lateral geniculate nucleus (LGN), magnocellular, parvocellular and koniocellular divisions. Due to the limited number of samples that could be amplified concurrently, amplifications were performed in 3 batches (batches A-C, containing 102, 119 and 10 experimental samples, respectively). To control for batch effects, common RNA pool control samples were amplified and hybridized in each batch. These included LCM extracted hippocampus CA3 samples from the current study and a whole rhesus brain RNA pool (Biochain). These control samples were hybridized in 6 replicates in batch A and B and in 3 replicates in batch C (3 replicates per 96 well plate).

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Functional annotation of genes differentially expressed between primary motor and prefrontal association cortices of macaque brain

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