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The identification of transcriptional targets of Ascl1 in oligodendrocyte development

Authors

  • Takaaki Ueno,

    1. Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan
    2. Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Junichi Ito,

    1. Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan
    2. Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Shinya Hoshikawa,

    1. Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan
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  • Yasuo Ohori,

    1. Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan
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  • Sayaka Fujiwara,

    1. Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Shinichi Yamamoto,

    1. Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan
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  • Toshiyuki Ohtsuka,

    1. Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Ryoichiro Kageyama,

    1. Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Masami Akai,

    1. Rehabilitation Hospital, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan
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  • Kozo Nakamura,

    1. Department of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Toru Ogata

    Corresponding author
    1. Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan
    • Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Saitama, Japan
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Abstract

The basic helix-loop-helix (bHLH) transcription factor Ascl1 plays crucial roles in both oligodendrocyte development and neuronal development; however, the molecular target of Ascl1 in oligodendrocyte progenitor cells (OPCs) remains elusive. To identify the downstream targets of Ascl1 in OPCs, we performed gene expression microarray analysis and identified Hes5 as a putative downstream target of Ascl1. In vivo analysis revealed that Ascl1 and Hes5 were coexpressed in early developmental oligodendrocytes in both the telencephalon and the ventral spinal cord. We also found that Hes5 expression was reduced in the OPCs of Ascl1 mutant mice. Furthermore, we demonstrated that Ascl1 directly binds to an E-box region within the Hes5 promoter and regulates Hes5 expression at the transcriptional level. Taken together, these in vivo and in vitro data suggest that Ascl1 induces Hes5 expression in a cell-autonomous manner. Considering the previously known function of Hes5 as a repressor of Ascl1, our data indicate that Hes5 is involved in the negative feedback regulation of Ascl1. © 2012 Wiley Periodicals, Inc.

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