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The regulatory role for the RNA binding polypyrimidine tract-binding (PTB) protein during neural development.

Research Project

Project/Area Number 22500286
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionThe University of Tokyo

Principal Investigator

YOSHIDA Nobuaki  東京大学, 医科学研究所, 教授 (10250341)

Co-Investigator(Kenkyū-buntansha) TOKUNAGA Akinori  大分大学, 全学研究推進機構, 助教 (70549451)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords発生工学 / 神経発生 / RNA splicing / ES細胞 / PTB / mRNA splicing
Research Abstract

PTB (Polypyrimidine tract binding) protein is a well-known multifunctional RNA binding protein, which can regulate mRNA stability, internal ribosome entry site (IRES) dependent translation, mRNA localization and alternative splicing (AS) by interacting with polypyrimidine rich sequences of target pre-RNAs and mRNAs. We have generated PTB knockout mice and null ESCs and found that PTB is essential for early mouse development and important for proliferation and differentiation of mouse ESCs. Its expression is observed various tissues and cells including neural stem cells (NSCs) and the expression was gradually down regulated during neural differentiation. Some in vitro studies demonstrated that knockdown of PTB leads to change of wide spread AS events similar to the change observed during neural differentiation. To explore the role of PTB in the developmental mouse brain, we generated conditional Ptb knockout mice (Nestin-Cre;Ptb flox/neo) and studied its phenotypes using histologlanalysis. Our findings show that the depletion of PTB in the developing mouse brain is eventually developed hydrocephalus and clearly reveal that PTB is important for the maintenance of adherens junctions in the dorsal telencephalon and might function in the regulation ofstem cell niche integrity upon the maintenace of NSCs.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (33 results)

All 2013 2012 2011 2010 Other

All Journal Article (19 results) (of which Peer Reviewed: 8 results) Presentation (10 results) Remarks (4 results)

  • [Journal Article] PTB deficiency causes the loss of adherens junctions in the dorsal telencehalon and leads to lethal2013

    • Author(s)
      柴嵜孝幸
    • Journal Title

      Cerebral Cortex

      Volume: 一(掲載予定) Issue: 8 Pages: 1-12

    • DOI

      10.1093/cercor/bhs161

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ras/MAPK signaling modulates VEGFR-3 expression through Ets-mediated p300 recruitment and histone acetylation on the Vegfr3 gene in lymphatic endothelial cells.2012

    • Author(s)
      Ichise T, Yoshida N, Ichise H.
    • Journal Title

      PLoS One.

      Volume: 7(12)

    • Related Report
      2012 Final Research Report
  • [Journal Article] PTB Deficiency Causes the Loss of Adherens Junctions in the Dorsal Telencephalon and Leads to Lethal Hydrocephalus.2012

    • Author(s)
      Shibasaki T, Tokunaga A, Sakamoto R, Sagara H, Noguchi S, Sasaoka T, Yoshida N.
    • Journal Title

      Cereb Cortex.

      Volume: [Epub ahead of print]

    • Related Report
      2012 Final Research Report
  • [Journal Article] Mastermind-like 1 (MamL1) and mastermind-like 3 (MamL3) are essential for Notch signaling in vivo.2011

    • Author(s)
      Oyama T, Harigaya K, Sasaki N, Okamura Y, Kokubo H, Saga Y, Hozumi K, Suganami A, Tamura Y, Nagase T, Koga H, Nishimura M, Sakamoto R, Sato M, Yoshida N, Kitagawa M.
    • Journal Title

      Development.

      Volume: 138(23) Pages: 5235-5246

    • Related Report
      2012 Final Research Report
  • [Journal Article] Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11(p58) in mouse embryonic stem cells.2011

    • Author(s)
      Ohno S, Shibayama M, Sato M, Tokunaga A, Yoshida N.
    • Journal Title

      Cell Cycle.

      Volume: 1;10(21) Pages: 3706-3713

    • Related Report
      2012 Final Research Report
  • [Journal Article] Obesity resistance and increased hepatic expression of catabolism-related mRNAs in Cnot3+/- mice.2011

    • Author(s)
      Morita M, Oike Y, Nagashima T, Kadomatsu T, Tabata M, Suzuki T, Nakamura T, Yoshida N, Okada M, Yamamoto T.
    • Journal Title

      EMBO J.

      Volume: 30(22) Pages: 4678-4691

    • Related Report
      2012 Final Research Report
  • [Journal Article] Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking.2011

    • Author(s)
      Fukui R, Saitoh S, Kanno A, Onji M, Shibata T, Ito A, Onji M, Matsumoto M, Akira S, Yoshida N, Miyake K.
    • Journal Title

      Immunity.

      Volume: 35(1) Pages: 69-81

    • Related Report
      2012 Final Research Report
  • [Journal Article] Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly.2011

    • Author(s)
      Fukuda T, Tokunaga A, Sakamoto R, YoshidaN.
    • Journal Title

      Mol Cell Neurosci.

      Volume: 46(3) Pages: 614-624

    • Related Report
      2012 Final Research Report
  • [Journal Article] (MamL1)/Mastermind-like 3 (MamL3) are essential for Notch signaling in vivo2011

    • Author(s)
      Oyama T, Harigaya K, Sasaki N, Okamura Y, Kokubo H, Saga Y, Hozumi K, Suganami A, Tamura Y, Nagase T, Koga H, Nishimura M, Sakamoto R, Sato M, Yoshida N, Kitagawa M
    • Journal Title

      Mastermind-like1

      Volume: 138 Issue: 23 Pages: 5235-5246

    • DOI

      10.1242/dev.062802

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11(p58) in mouse embryonic stem cells2011

    • Author(s)
      Ohno S, Shibayama M, Sato M, Tokunaga A, Yoshida N
    • Journal Title

      Cell Cycle

      Volume: 10(21) Issue: 21 Pages: 3706-3713

    • DOI

      10.4161/cc.10.21.17903

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Obesity resistance and increased hepatic expression of catabolism- related mRNAs in Cnot3+/- mice2011

    • Author(s)
      Morita M, Oike Y, Yamamoto T (10名)
    • Journal Title

      EMBO J

      Volume: Vol.30 Issue: 22 Pages: 4678-4691

    • DOI

      10.1038/emboj.2011.320

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unc93B1 restricts systemic lethal inflammation by orchestrating Toll-like receptor 7 and 9 trafficking2011

    • Author(s)
      Fukui R
    • Journal Title

      Immunity

      Volume: 35 Issue: 1 Pages: 69-81

    • DOI

      10.1016/j.immuni.2011.05.010

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fbx110/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly.2011

    • Author(s)
      Fukuda T, Tokunaga A, Sakamoto R, Yoshida N.
    • Journal Title

      Mol Cell Neurosci.

      Volume: 46(3) Pages: 614-624

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nucleoredoxin sustains Wnt/β-catenin signaling by retaining a pool of inactive dishevelled protein.2010

    • Author(s)
      Funato Y, Terabayashi T, Sakamoto R, Okuzaki D, Ichise H, Nojima H, Yoshida N, Miki H.
    • Journal Title

      Curr Biol.

      Volume: 20(21) Pages: 1945-1952

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Journal Article] Nucleoredoxin negatively regulates Toll-like receptor 4 signaling via recruitment of flightless-I to myeloid differentiation primary response gene (88).2010

    • Author(s)
      Hayashi T, Funato Y, Terabayashi T, Morinaka A, Sakamoto R, Ichise H, Fukuda H, Yoshida N, Miki H.
    • Journal Title

      J Biol Chem.

      Volume: 285(24) Pages: 18586-18593

    • Related Report
      2012 Final Research Report
  • [Journal Article] N- and Kras cooperatively regulate lymphatic vessel growth by modulating VEGFR3 expression in lymphatic endothelial cells in mice.2010

    • Author(s)
      Ichise T, Yoshida N, Ichise H. H-
    • Journal Title

      Development.

      Volume: 137(6) Pages: 1003-1013

    • Related Report
      2012 Final Research Report
  • [Journal Article] An FGF4-FRS2alpha-Cdx2 axis in trophoblast stem cells induces Bmp4 to regulate proper growth of early mouse embryos.2010

    • Author(s)
      Murohashi M, Nakamura T, Tanaka S, Ichise T, Yoshida N, Yamamoto T, Shibuya M, Schlessinger J, Gotoh N.
    • Journal Title

      Stem Cells.

      Volume: 28(1) Pages: 113-121

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Journal Article] Nucleoredoxin negatively regulates Toll-like receptor 4 signaling viarecruitment of flightless-I to myeloid differentiation primary response gene (88).2010

    • Author(s)
      Hayashi T, Funato Y, Terabayashi T, Morinaka A, Sakamoto R, Ichise H, Fukuda H, Yoshida N, Miki H.
    • Journal Title

      J Biol Chem.

      Volume: 285(24) Pages: 18586-18593

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] H-, N- and Kras cooperatively regulate lymphatic vessel growth by modulating VEGFR3 expression in lymphatic endothelial cells in mice.2010

    • Author(s)
      Ichise T, Yoshida N, Ichise H.
    • Journal Title

      Development.

      Volume: 137(6) Pages: 1003-1013

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] The Role of PTB, Alternative Splicing Regulation Factor, for Spermatogenesis2012

    • Author(s)
      Takijiri T, et al.
    • Organizer
      第35回 日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Mammal-specific domain in Brn-2 induce changes of neurotransmitter expression2011

    • Author(s)
      Atsushi Igarashi, Aya Matsushima, Makoto Nasu, Denetsu Sutoo, Kayo Akiyama, Naoyuki Koduki, Nobuaki Yoshida, Shintaroh Ueda
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜・横浜・日本
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 初期発生におけるポリコーム群遺伝子rybpの機能解析2011

    • Author(s)
      川上絵理, 徳永暁憲, 坂本怜子, 吉田進昭
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜・横浜・日本
    • Year and Date
      2011-12-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] 初期発生におけるポリコーム群遺伝子rybpの機能解析2011

    • Author(s)
      川上絵理、徳永暁憲、坂本怜子、吉田進昭
    • Organizer
      第34回 日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-02-14
    • Related Report
      2012 Final Research Report
  • [Presentation] Targeted disruption of Fbxl10 causes neural tube defects resulting in exencephaly2010

    • Author(s)
      福田 剛、 徳永 暁憲、吉田 進昭
    • Organizer
      第33回 日本分子生物学会 , 第 83回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-08
    • Related Report
      2012 Final Research Report
  • [Presentation] PTB deficiency in the brain disrupts dorsal neuroepithelium of the lateral ventricles and leads lethal hydrocephalus2010

    • Author(s)
      柴嵜 孝幸、 徳永 暁憲、 吉田 進昭
    • Organizer
      第33回日本分子生物学会,第83回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-08
    • Related Report
      2012 Final Research Report
  • [Presentation] Targeted disruption of Fbx110 causes neural tube defects resulting in ex-encephaly2010

    • Author(s)
      福田剛、徳永暁憲, 吉田進昭
    • Organizer
      第33回日本分子生物学会第83回日本生化学会大会
    • Place of Presentation
      神戸国際展示場
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] PTB deficiency in the brain disrupts dorsal neuroepithelium of the lateral ventricles and leads lethal hydrocephalus2010

    • Author(s)
      柴嵜孝幸, 徳永暁憲, 吉田進昭
    • Organizer
      第33回日本分子生物学会第83回日本生化学会大会
    • Place of Presentation
      神戸国際展示場
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Functional analysis of nPTB,nervous system specific RNA binding protein2010

    • Author(s)
      正木 信也、 徳永 暁憲、吉田 進昭
    • Organizer
      第33回日本分子生物学会 , 第 83 回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2012 Final Research Report
  • [Presentation] Functional analysis of nPTB, nervous system specific RNA binding protein2010

    • Author(s)
      正木信也, 徳永暁憲, 吉田進昭
    • Organizer
      第33回日本分子生物学会第83回日本生化学会大会
    • Place of Presentation
      神戸国際展示場
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/cem_ger/HPidenshikinou/main.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 東京大学医科学研究所 システム疾患モデル研究センター 発生工学研究分野

    • URL

      http://www.ims.u-tokyo.ac.jp/cem_ger/HPidenshikinou/main.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/cem_ger/HPidenshikinou/main.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/cem_ger/HPidenshikinou/main.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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