Analysis for a neural differentiation regulatory factor, Musashi1

• Project/Area Number: 24500447
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kyushu University (2013-2014); Keio University (2012)
• Principal Investigator: HORISAWA Kenichi 九州大学, 生体防御医学研究所, 助教 (70424207)
• Co-Investigator(Kenkyū-buntansha): 今井 貴雄 慶應義塾大学, 医学部生理学教室, 助教 (10383712) ; 芝田 晋介 慶應義塾大学, 医学部生理学教室, 講師 (70407089)
• Co-Investigator(Renkei-kenkyūsha): 岡野 栄之 慶應義塾大学, 医学部生理学教室, 教授 (60160694) ; 土居 信英 慶應義塾大学, 理工学部生命情報学科, 准教授 (50327673)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Musashi1 / RNA結合タンパク質 / 神経発生 / 神経回路 / 未分化維持 / 翻訳制御 / 転写後制御 / 神経分化 / Musashi / Dcc / Dcx / 分化 / 幹細胞 / 再生医学

Outline of Final Research Achievements

Musashi1 (Msi1) is a RNA-binding, which is highly expressed in neural stem/progenitor cells and is responsible for stem cell maintenance and differentiation. The main function of Msi1 is to regulate the expression of its target mRNAs through translational up/down-regulation.
In search for novel Msi1 targets, in vitro SELEX selection was performed from a mouse embryonic brain mRNA library, and a 3’ UTR fragment of dcc was obtained. Dcc is a transmembrane receptor expressed on the growth cones of neurons, and it guides axons and cells in response to Netrin1.
In this project, in vitro and in cultured cell experiments clearly identified that the dcc mRNA is a direct target of Msi1, and is suppressed their translation through a canonical molecular machinery. Now, we are analyzing the connection between the molecular mechanism and neural development by using Msi1-KO mice.

Research Products

• [Journal Article] Connectomics: Comprehensive approaches for whole brain mapping (2015)
  • Author(s): Shibata S, Komaki Y, Seki F, Inouye MO, Nagai T, Okano H.
  • Journal Title: Microscopy Volume: 64 Pages: 57-67
  • DOI: 10.1093/jmicro/dfu103
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Specific and quantitative labeling of biomolecules using click chemistry. (2014)
  • Author(s): Horisawa K.
  • Journal Title: Front Physiol. Volume: 5 Pages: 457-457
  • DOI: 10.3389/fphys.2014.00457
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rfx Transcription Factors Control Musashi1 Transcription in Mouse Neural Stem/Progenitor Cells (2014)
  • Author(s): Kawase S, Kuwako K, Imai T, Renault-Mihara F, Yaguchi K, Itohara S, Okano H.
  • Journal Title: Stem Cells and Development Volume: 23 Pages: 2250-2261
  • DOI: 10.1089/scd.2014.0219
  • Peer Reviewed
• [Journal Article] Migration and differentiation of transplanted enteric neural crest-derived cells in murine model of Hirschsprung’s disease. (2014)
  • Author(s): Nishikawa R, Hotta R, Shimojima N, Shibata S, Nagoshi N, Nakamura M, Matsuzaki Y, Okano HJ, Kuroda T, Okano H, Morikawa Y.
  • Journal Title: Cytotechnology Volume: Sep 18
  • DOI: 10.1007/s10616-014-9754-8
  • Peer Reviewed
• [Journal Article] Yb integrates piRNA intermediates and processing factors into perinuclear bodies to enhance piRISC assembly (2014)
  • Author(s): Murota Y, Ishizu H, Nakagawa S, Iwasaki YW, Shibata S, Kamatani MK, Saito K, Okano H, Siomi H, Siomi MC.
  • Journal Title: Cell Rep Volume: 8 Pages: 103-113
  • DOI: 10.1016/j.celrep.2014.05.043
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of ER stress in dysmyelination of Pelizaeus-Merzbacher disease with PLP1 missense mutations shown by iPSC-derived oligodendrocytes. (2014)
  • Author(s): Numasawa-Kuroiwa Y, Okada Y, Shibata S, Kishi N, Akamatsu W, Shoji M, Nakanishi A, Oyama M, Oasaka H, Inoue K, Takahashi K, Yamanaka S, Kosaki K, Takahashi T, Okano H
  • Journal Title: StemCellReports Volume: 2 Pages: 1-14
  • DOI: 10.1016/j.stemcr.2014.03.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Global gene expression analysis following spinal cord injury in non-human primates. (2014)
  • Author(s): Nishimura S, Sasaki T, Shimizu A, Yoshida K, Iwai H, Koya I, Kobayashi Y, Iakura G, Shibata S, Ebise H, Horiuchi K, Kudoh J, Toyama Y, Anderson AJ, Okano H, Nakamura M.
  • Journal Title: Exp Neurol. Volume: 261 Pages: 171-179
  • DOI: 10.1016/j.expneurol.2014.05.021
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of ER stress in dysmyelination of Pelizaeus-Merzbacher disease with PLP1 missense mutations shown by iPSC-derived oligodendrocytes (2014)
  • Author(s): Kuroiwa-Numasawa Y, Okada Y, Shibata S, Kishi N, Akamatsu W, Shoji M, Nakanishi A, Oyama M, Osaka H, Inoue K, Takahashi K, Yamanaka S, Kosaki K, Takahashi T, Okano H
  • Journal Title: Stem Cell Reports Volume: 未定
  • Peer Reviewed
• [Journal Article] Rewiring of regenerated axons by combining treadmill training with semaphorin3A inhibition. (2014)
  • Author(s): Zhang L, Kaneko S, Kikuchi K, Sano A, Maeda M, Kishino A, Shibata S, Mukaino M, Toyama Y, Liu M, Kimura T, Okano H, Nakamura M
  • Journal Title: Molecular Brain Volume: 7 Pages: 14-14
  • DOI: 10.1186/1756-6606-7-14
  • Peer Reviewed
• [Journal Article] Inflammatory cascades mediate synapse elimination in spinal cord compression. (2014)
  • Author(s): Takano M, Kawabata S, Komaki Y, Shibata S, Hikishima K, Toyama Y, Okano H, Nakamura M.
  • Journal Title: Journal of Neuroinflammation Volume: 11 Pages: 40-40
  • DOI: 10.1186/1742-2094-11-40
  • Peer Reviewed
• [Journal Article] MIP-2A is a novel target of an anilinoquinazoline derivative for inhibition of tumour cell proliferation. (2013)
  • Author(s): Tokunaga M, Shiheido H, Tabata N, Sakuma-Yonemura Y, Takashima H, Horisawa K, Doi N, Yanagawa H.
  • Journal Title: PLoS One. Volume: 8
  • DOI: 10.1371/journal.pone.0076774
  • Peer Reviewed
• [Journal Article] Hereditary spastic paraplegia protein spartin is an FK506-binding protein identified by mRNA display. (2013)
  • Author(s): Tokunaga M, Shiheido H, Hayakawa I, Utsumi A, Takashima H, Doi N, Horisawa K, Sakuma-Yonemura Y, Tabata N, Yanagawa H.
  • Journal Title: Chemistry & Biology Volume: 20 Pages: 935-942
  • DOI: 10.1016/j.chembiol.2013.05.011
  • Peer Reviewed
• [Journal Article] The long non-coding RNA nuclear-enriched abundant transcript 1_2 induces paraspeckle formation in the motor neuron during the early phase of amyotrophic lateral sclerosis. (2013)
  • Author(s): Nishimoto, Y., Nakagawa, S., Hirose, T., Okano, H. J., Takao, M., Shibata, S., Suyama, S., Kuwako, K., Imai, T., Murayama, S., Suzuki, N., and Okano, H
  • Journal Title: Molecular Brain Volume: 6 Pages: 31-31
  • DOI: 10.1186/1756-6606-6-31
  • Peer Reviewed
• [Journal Article] Differential cellular localization of antioxidant enzymes in the trigeminal ganglion. (2013)
  • Author(s): Sato H, Shibata M, Shimizu T, Shibata S, Haruki T, Ebine T, Kuroi T, Iwashita T, Funakubo M, Kayama Y, Akazawa C, Wajima K, Nakagawa T. Okano H. Suzuki N
  • Journal Title: Neuroscience. Volume: 248 Pages: 345-348
  • DOI: 10.1016/j.neuroscience.2013.06.010
  • Peer Reviewed
• [Journal Article] Sema3A regulates bone-mass accrual through sensory innervations. (2013)
  • Author(s): Fukuda T, Takeda S, Xu R, Ochi H, Sunamura S, Sato T, Shibata S, Yoshida Y, Gu Z, Kimura A, Ma C, Xu C, Bando W, Fujita K, Shinomiya K, Hirai T, Asou Y, Enomoto M, Okano H, Okawa A, Itoh H
  • Journal Title: Nature Volume: 497 Pages: 490-3
  • DOI: 10.1038/nature12115
  • Peer Reviewed
• [Journal Article] SOX10 is a novelmarker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis. (2013)
  • Author(s): Ohtomo R, Mori T, Shibata S, Tsuta K, Maeshima M, Akazawa C, Honda K, Yamada T, Yoshimoto S, Asai M, Okano H, Kanai Y, Tsuda H
  • Journal Title: Mod Pathol Volume: Aug;26(8): Pages: 1041-1050
  • DOI: 10.1038/modpathol.2013.54
  • Peer Reviewed
• [Journal Article] Musashi-1 Post-Transcriptionally Enhances Phosphotyrosine-Binding Domain-Containing m-Numb Protein Expression in Regenerating Gastric Mucosa. (2013)
  • Author(s): Tetsufumi Takahashi
  • Journal Title: PLoS One Volume: 8 Pages: 1-13
  • DOI: 10.1371/journal.pone.0053540
  • Peer Reviewed
• [Journal Article] RNA-Binding Protein Musashi1 Modulates Glioma Cell Growth through the Post-Transcriptional Regulation of Notch and PI(3) Kinase/Akt Signaling Pathway. (2012)
  • Author(s): Muto J, Imai T, Ogawa D, Nishimoto Y, Okada Y, Mabuchi Y, Kawase T, Iwanami A, Mischel PS, Saya H, Yoshida K, Matsuzaki Y, Okano H
  • Journal Title: PLoS One. Volume: 7(3)
  • DOI: 10.1371/journal.pone.0033431
  • Peer Reviewed
• [Journal Article] RNA結合タンパク質による遺伝子制御と神経発生・神経機能 (2012)
  • Author(s): 今井貴雄、岡野栄之
  • Journal Title: 細胞工学 Volume: 31 Pages: 668-674
  • Peer Reviewed
• [Presentation] A novel chemical tool for proteomic analysis of translational control (2013)
  • Author(s): Horisawa K., Miyazawa T., Ohkawa K., Oka K. and Doi N.
  • Organizer: The 12th Human Proteome Organisation World Congress
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] 翻訳調節による遺伝子発現制御の研究と解析技術の開発 (2013)
  • Author(s): 堀澤健一
  • Organizer: 筑波大学大学院生命環境科学研究科セミナー 動物細胞バイオテクノロジー
  • Place of Presentation: 筑波大学（つくば市）
  • Invited
• [Presentation] RNA-binding protein Msi1 regulates the expression of an axon guidance receptor through translational repression (2012)
  • Author(s): Hara H., Horisawa K., Yanagawa H., Doi N.
  • Organizer: Translational Control
  • Place of Presentation: NewYork
• [Presentation] 神経発生におけるRNA結合タンパク質Msi1による翻訳制御 (2012)
  • Author(s): 原裕恵、堀澤健一、松尾薫、柳川弘志、土居信英
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Book] 細胞工学別冊 ダイレクトリプログラミング ：目的細胞別 遺伝子導入・培養条件・機能解析リファレンス (2015)
  • Author(s): 堀澤健一、鈴木淳史（鈴木淳史・監修）
  • Total Pages: 119
  • Publisher: 学研メディカル秀潤社
• [Book] Neural Stem Cells and Therapy (2012)
  • Author(s): Horisawa K. and Yanagawa H.
  • Total Pages: 17
  • Publisher: InTech