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開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

DISC1 regulates differentiation of oligodendrocytes

  • P2-322
  • 伊藤 彰 / Akira Ito:1 服部 剛志 / Tsuyoshi Hattori:2 清水 尚子 / Shoko Shimizu:3 小山 佳久 / Yoshihisa Koyama:4 江本 尚代 / Hisayo Emoto:5 松本 裕司 / Yuji Matsumoto:5 熊本 奈都子 / Natsuko Kumamoto:6 山田 康平 / Kohei Yamada:7 高村 明孝 / Hironori Takamura:8 松崎 伸介 / Shinsuke Matsuzaki:8,9 片山 泰一 / Taiichi Katayama:8 遠山 正彌 / Masaya Tohyama:3,8,9 
  • 1:大阪大院・医・分子精神神経学 / Dept Mol Neuropsychiatry, Osaka Univ, Osaka, Japan 2:金沢大院・医薬保健・神経分子標的学 / Dept of Neuroanat, Kanazawa Univ, Ishikawa, Japan 3:近畿大・東洋医学研・分子脳科学 / Div Mol Brain Sci, Kinki Univ, Osaka, Japan 4:大阪大院・医・神経細胞生物学 / Dept Neuroscience and Cell Biology, Osaka Univ, Osaka, Japan 5:大日本住友製薬・研究本部 / Drug Res Div, Dainippon Sumitomo Pharma Co, Ltd, Osaka, Japan 6:名市大院・医・機能組織学 / Dept Neurobiol and Anat, Nagoya City Univ, Aichi, Japan 7:浜松医大・子どものこころの発達研究センター / Res Ctr for Child Mental Develop, Hamamatsu Univ School Med, Shizuoka, Japan 8:大阪大・金沢大・浜松医大・千葉大・福井大・連合小児発達・分子生物遺伝学 / Dept Child Develop & Mol Brain Sci, United Grad School of Child Develop, Osaka Univ, Kanazawa Univ, Hamamatsu Univ School Med, Chiba Univ and Univ Fukui, Osaka,  9:大阪大院・医・神経機能形態学 / Dept Anat and Neurosci, Osaka Univ, Osaka, Japan 

Disrupted-in-schizophrenia 1 (DISC1) is a gene disrupted by a translocation that segregates with major psychiatric disorders, including schizophrenia, recurrent major depression and bipolar affective disorder, in a Scottish family. Here we report that mammalian DISC1 endogenously expressed in oligodendroglial lineage cells negatively regulates differentiation of oligodendrocyte precursor cells into oligodendrocytes. DISC1 expression was detected in oligodendrocytes of the mouse corpus callosum at P14 and P70. DISC1 mRNA was expressed in primary cultured rat cortical oligodendrocyte precursor cells and decreased when oligodendrocyte precursor cells was induced to differentiate by PDGF deprivation. Immunocytochemical analysis showed that overexpressed DISC1 was localized in the cell bodies and processes of oligodendrocyte precursor cells and oligodendrocytes. We show that expression of the myelin related markers, CNPase and MBP, as well as the number of cells with matured oligodendrocyte morphology, were decreased following full length DISC1 overexpression. Conversely, both expression of CNPase and the number of oligodendrocytes with a mature morphology were increased following knockdown of endogenous DISC1 by RNA interference. Overexpression of a truncated form of DISC1 also resulted in an increase in expression of myelin related proteins and the number of mature oligodendrocytes, potentially acting via a dominant negative mechanism. We also identified involvement of Sox10 and Nkx2.2 in the DISC1 regulatory pathway of oligodendrocyte differentiation, both well-known transcription factors involved in the regulation of myelin genes.

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