Neurochemical Research

, Volume 38, Issue 1, pp 133–140 | Cite as

Functional Annotation of Genes Differentially Expressed Between Primary Motor and Prefrontal Association Cortices of Macaque Brain

  • Toshio Kojima
  • Noriyuki Higo
  • Akira Sato
  • Takao Oishi
  • Yukio Nishimura
  • Tatsuya Yamamoto
  • Yumi Murata
  • Kimika Yoshino-Saito
  • Hirotaka Onoe
  • Tadashi Isa
Original Paper


DNA microarray-based genome-wide transcriptional profiling and gene network analyses were used to characterize the molecular underpinnings of the neocortical organization in rhesus macaque, with particular focus on the differences in the functional annotation of genes in the primary motor cortex (M1) and the prefrontal association cortex (area 46 of Brodmann). Functional annotation of the differentially expressed genes showed that the list of genes selectively expressed in M1 was enriched with genes involved in oligodendrocyte function, and energy consumption. The annotation appears to have successfully extracted the characteristics of the molecular structure of M1.


DNA microarray Gene expression Gene network Primary motor area Prefrontal area Primate, rhesus monkey 



We are grateful to Ms. Mami Kishima (RIKEN OSC) for her technical advice. This study was supported by Core Research for Evolutionary Science and Technology (CREST) of Japan Science and Technology Agency (JST).

Supplementary material

11064_2012_900_MOESM1_ESM.pptx (255 kb)
Figure S1. Expression profiles of the M1 selectively expressed genes. Normalized intensity values of each sample are expressed as a heatmap. Gene symbols are described on the left Supplementary material 1 (PPTX 254 kb)
11064_2012_900_MOESM2_ESM.pptx (142 kb)
Figure S2. Expression profiles of the A46 selectively expressed genes. Supplementary material 2 (PPTX 142 kb)
11064_2012_900_MOESM3_ESM.pptx (530 kb)
Figure S3. Significant gene networks of the M1 selectively expressed genes. Networks were identified using the Ingenuity program. In each network, solid lines indicate direct interactions, dashed lines indicate indirect interactions, lines without arrowheads indicate binding, and arrows connecting 2 genes indicate directional functionality, whereby 1 gene acts on the other based on the direction of the arrow. Node shapes represent different gene families/groups: square (solid line), cytokine; square (dashed line), growth factor; rectangle (solid line), G-protein coupled receptor; rectangle (dashed line), ion channel; double circle, group or complex; triangle, kinase; diamond (vertical), enzyme; diamond (horizontal), peptidase; hexagon, translation regulator; trazoid, transporter; oval (horizontal), transcription regulator; and oval (vertical), transmembrane receptor. Proteins identified in this analysis are shaded Supplementary material 3 (PPTX 529 kb)
11064_2012_900_MOESM4_ESM.pptx (392 kb)
Figure S4 (PPTX 392 kb)
11064_2012_900_MOESM5_ESM.xlsx (16 kb)
Table S1 (XLSX 15 kb)
11064_2012_900_MOESM6_ESM.xlsx (14 kb)
Table S2 (XLSX 13 kb)


  1. 1.
    Bernard A, Lubbers LS, Tanis KQ, Luo R, Podtelezhnikov AA, Finney EM, McWhorter MM, Serikawa K, Lemon T, Morgan R, Copeland C, Smith K, Cullen V, Davis-Turak J, Lee CK, Sunkin SM, Loboda AP, Levine DM, Stone DJ, Hawrylycz MJ, Roberts CJ, Jones AR, Geschwind DH, Lein ES (2012) Transcriptional architecture of the primate neocortex. Neuron 73:1083–1099PubMedCrossRefGoogle Scholar
  2. 2.
    Yamamori T (2011) Selective gene expression in regions of primate neocortex: implications for cortical specialization. Prog Neurobiol 94:201–222PubMedCrossRefGoogle Scholar
  3. 3.
    Sato A, Nishimura Y, Oishi T, Higo N, Murata Y, Onoe H, Saito K, Tsuboi F, Takahashi M, Isa T, Kojima T (2007) Differentially expressed genes among motor and prefrontal areas of macaque neocortex. Biochem Biophys Res Commun 362:665–669PubMedCrossRefGoogle Scholar
  4. 4.
    Kojima T, Ueda Y, Adati N, Kitamoto A, Sato A, Huang MC, Noor J, Sameshima H, Ikenoue T (2010) Gene network analysis to determine the effects of antioxidant treatment in a rat model of neonatal hypoxic-ischemic encephalopathy. J Mol Neurosci 42:154–161PubMedCrossRefGoogle Scholar
  5. 5.
    Jimenez-Marin A, Collado-Romero M, Ramirez-Boo M, Arce C, Garrido J (2009) Biological pathway analysis by ArrayUnlock and Ingenuity Pathway Analysis. BMC Proc 3:S6PubMedCrossRefGoogle Scholar
  6. 6.
    Francis JS, Olariu A, McPhee SW, Leone P (2006) Novel role for aspartoacylase in regulation of BDNF and timing of postnatal oligodendrogenesis. J Neurosci Res 84:151–169PubMedCrossRefGoogle Scholar
  7. 7.
    Calaora V, Rogister B, Bismuth K, Murray K, Brandt H, Leprince P, Marchionni M, Dubois-Dalcq M (2001) Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro. J Neurosci 21:4740–4751PubMedGoogle Scholar
  8. 8.
    Cai J, Qi Y, Hu X, Tan M, Liu Z, Zhang J, Li Q, Sander M, Qiu M (2005) Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron 45:41–53PubMedCrossRefGoogle Scholar
  9. 9.
    Wang SZ, Dulin J, Wu H, Hurlock E, Lee SE, Jansson K, Lu QR (2006) An oligodendrocyte-specific zinc-finger transcription regulator cooperates with Olig2 to promote oligodendrocyte differentiation. Development 133:3389–3398PubMedCrossRefGoogle Scholar
  10. 10.
    Bansal R, Winkler S, Bheddah S (1999) Negative regulation of oligodendrocyte differentiation by galactosphingolipids. J Neurosci 19:7913–7924PubMedGoogle Scholar
  11. 11.
    Novgorodov AS, El Alwani M, Bielawski J, Obeid LM, Gudz TI (2007) Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration. FASEB J 21:1503–1514PubMedCrossRefGoogle Scholar
  12. 12.
    Tiwari-Woodruff SK, Buznikov AG, Vu TQ, Micevych PE, Chen K, Kornblum HI, Bronstein JM (2001) Osp/Claudin-11 forms a complex with a novel member of the tetraspanin super family and β1 integrin and regulates proliferation and migration of oligodendrocytes. J Cell Biol 153:295–306PubMedCrossRefGoogle Scholar
  13. 13.
    Frank M, Schaeren-Wiemers N, Schneider R, Schwab ME (1999) Developmental expression pattern of the myelin ProteolipiMAL indicates different functions of MAL for immature Schwann cells and in a late step of CNS myelinogenesis. J Neurochem 73:587–597PubMedCrossRefGoogle Scholar
  14. 14.
    Schaeren-Wiemers N, Valenzuela DM, Frank M, Schwab ME (1995) Characterization of a rat gene, rMAL, encoding a protein with four hydrophobic domains in central and peripheral myelin. J Neurosci 15:5753–5764PubMedGoogle Scholar
  15. 15.
    Emery B, Agalliu D, Cahoy JD, Watkins TA, Dugas JC, Mulinyawe SB, Ibrahim A, Ligon KL, Rowitch DH, Barres BA (2009) Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination. Cell 138:172–185PubMedCrossRefGoogle Scholar
  16. 16.
    Potter KA, Kern MJ, Fullbright G, Bielawski J, Scherer SS, Yum SW, Li JJ, Cheng H, Han X, Venkata JK, Akbar Ali Khan P, Rohrer B, Hama H (2011) Central nervous system dysfunction in a mouse model of Fa2 h deficiency. Glia 59:1009–1021PubMedCrossRefGoogle Scholar
  17. 17.
    Anzini P, Neuberg DHH, Schachner M, Nelles E, Willecke K, Zielasek J, Toyka KV, Suter U, Martini R (1997) Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin 32. J Neurosci 17:4545–4551PubMedGoogle Scholar
  18. 18.
    King RHM, Chandler D, Lopaticki S, Huang D, Blake J, Muddle JR, Kilpatrick T, Nourallah M, Miyata T, Okuda T, Carter KW, Hunter M, Angelicheva D, Morahan G, Kalaydjieva L (2011) Ndrg1 in development and maintenance of the myelin sheath. Neurobiol Dis 42:368–380PubMedCrossRefGoogle Scholar
  19. 19.
    Okuda T, Higashi Y, Kokame K, Tanaka C, Kondoh H, Miyata T (2004) Ndrg1-deficient mice exhibit a progressive demyelinating disorder of peripheral nerves. Mol Cel Biol 24:3949–3956CrossRefGoogle Scholar
  20. 20.
    Jansson M, Panoutsakopoulou V, Baker J, Klein L, Cantor H (2002) Cutting edge: attenuated experimental autoimmune encephalomyelitis in eta-1/osteopontin-deficient mice. J Immunol 168:2096–2099PubMedGoogle Scholar
  21. 21.
    Preuss TM, Goldman-Rakic PS (1991) Architectonics of the parietal and temporal association cortex in the strepsirhine primate Galago compared to the anthropoid primate Macaca. J Comp Neurol 310:475–506PubMedCrossRefGoogle Scholar
  22. 22.
    Chernogubova E, Hutchinson DS, Nedergaard J, Bengtsson T (2005) Alpha1- and beta1-adrenoceptor signaling fully compensates for beta3-adrenoceptor deficiency in brown adipocyte norepinephrine-stimulated glucose uptake. Endocrinol 146:2271–2284CrossRefGoogle Scholar
  23. 23.
    Cantó C, Suárez E, Lizcano JM, Alessi DR, Griñó E, Shepherd PR, Fryer L, Carling D, Bertran J, Palacín M, Zorzano A, Guma A (2004) Neuregulin signaling on glucose transport in muscle cells. J Biol Chem 279:12260–12268PubMedCrossRefGoogle Scholar
  24. 24.
    Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Hussain M (2008) Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and glucagon-like peptide 1–independent pathways. Circulation 117:2340–2350PubMedCrossRefGoogle Scholar
  25. 25.
    Egan JM, Montrose-Rafizadeh C, Wang Y, Bernier M, Roth J (1994) Glucagon-like peptide-1(7–36) amide (GLP-1) enhances insulin-stimulated glucose metabolism in 3T3-L1 adipocytes: one of several potential extrapancreatic sites of GLP-1 action. Endocrinol 135:2070–2075CrossRefGoogle Scholar
  26. 26.
    Matelli M, Luppino G, Rizzolatti G (1985) Patterns of cytochrome oxidase activity in the frontal agranular cortex of the macaque monkey. Behav Brain Res 18:125–136PubMedCrossRefGoogle Scholar
  27. 27.
    Wong-Riley MTT (1989) Cytochrome oxidase: an endogenous metabolic marker for neuronal activity. Trends Neurosci 12:94–101PubMedCrossRefGoogle Scholar
  28. 28.
    Nickols HH, Shah VN, Chazin WJ, Limbird LE (2004) Calmodulin interacts with the V2 vasopressin receptor. J Biol Chem 279:46969–46980PubMedCrossRefGoogle Scholar
  29. 29.
    Pollock AS, Santiesteban HL (1995) Calbindin expression in renal tubular epithelial cells. Altered sodium phosphate co-transport in association with cytoskeletal rearrangement. J Biol Chem 270:16291–16301PubMedCrossRefGoogle Scholar
  30. 30.
    Lelouvier B, Puertollano R (2011) Mucolipin-3 regulates luminal calcium, acidification, and membrane fusion in the endosomal pathway. J Biol Chem 286:9826–9832PubMedCrossRefGoogle Scholar
  31. 31.
    Kim J, Ghosh S, Liu H, Tateyama M, Kass RS, Pitt GS (2004) Calmodulin mediates Ca2 + sensitivity of sodium channels. J Biol Chem 279:45004–45012PubMedCrossRefGoogle Scholar
  32. 32.
    Graupner M, Brunel N (2012) Calcium-based plasticity model explains sensitivity of synaptic changes to spike pattern, rate, and dendritic location. Proc Natl Acad Sci USA 109:3991–3996PubMedCrossRefGoogle Scholar
  33. 33.
    Blumenfeld RS, Ranganath C (2006) Dorsolateral prefrontal cortex promotes long-term memory formation through its role in working memory organization. J Neurosci 26:916–925PubMedCrossRefGoogle Scholar
  34. 34.
    Rossi S, Cappa SF, Babiloni C, Pasqualetti P, Miniussi C, Carducci F, Babiloni F, Rossini PM (2001) Prefontal cortex in long-term memory: an “interference” approach using magnetic stimulation. Nat Neurosci 4:948–952PubMedCrossRefGoogle Scholar
  35. 35.
    Croxson PL, Kyriazis DA, Baxter MG (2011) Cholinergic modulation of a specific memory function of prefrontal cortex. Nat Neurosci 14:1510–1512PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Toshio Kojima
    • 1
    • 2
    • 3
  • Noriyuki Higo
    • 2
    • 4
    • 5
  • Akira Sato
    • 2
    • 3
  • Takao Oishi
    • 2
    • 6
  • Yukio Nishimura
    • 2
    • 5
    • 8
  • Tatsuya Yamamoto
    • 2
    • 4
    • 7
  • Yumi Murata
    • 4
  • Kimika Yoshino-Saito
    • 2
    • 4
    • 8
  • Hirotaka Onoe
    • 2
    • 9
  • Tadashi Isa
    • 2
    • 8
    • 10
  1. 1.Research Equipment CenterHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Core Research for Evolutional Science and Technology (CREST)Japan Science and Technology Agency (JST)KawaguchiJapan
  3. 3.Computational Systems Biology Research Group, Advanced Science InstituteRIKENYokohamaJapan
  4. 4.Neuroscience Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  5. 5.Precursory Research for Embryonic Science and Technology (PREST)Japan Science and Technology Agency (JST)KawaguchiJapan
  6. 6.Department of Cellular and Molecular Biology, Primate Research InstituteKyoto UniversityInuyamaJapan
  7. 7.Graduate School of Comprehensive Human ScienceUniversity of TsukubaTsukubaJapan
  8. 8.Department of Developmental PhysiologyNational Institute for Physiological Sciences (NIPS), National Institutes of Natural SciencesOkazakiJapan
  9. 9.Functional Probe Research Laboratory, Center for Molecular Imaging ScienceRIKENKobeJapan
  10. 10.School of Life ScienceThe Graduate University for Advanced Studies (SOKENDAI)HayamaJapan

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