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RNA-mediated regulatory mechanisms involved in germ cell development

Research Project

Project/Area Number 26251025
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionNational Institute of Genetics

Principal Investigator

Saga Yumiko  国立遺伝学研究所, 系統生物研究センター, 教授 (50221271)

Co-Investigator(Renkei-kenkyūsha) KATO Yuzuru  国立遺伝学研究所, 系統生物研究センター, 助教 (60570249)
AJIMA Rieko  国立遺伝学研究所, 系統生物研究センター, 助教 (10615066)
NINOMIYA Yoichirou  国立遺伝学研究所, 系統生物研究センター, 特任研究員 (90237777)
SUZUKI Atsushi  横浜国立大学, 工学(系)研究科(研究院), 准教授 (60467058)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥40,430,000 (Direct Cost: ¥31,100,000、Indirect Cost: ¥9,330,000)
Fiscal Year 2016: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2015: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2014: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
KeywordsNanos2 / Nanos3 / Dnd1 / germ cell / testis / spermatogenesis / P-body / RNA結合タンパク質 / 雄性分化 / 生殖細胞 / Nanso2 / 始原生殖細胞 / 性分化 / GS細胞 / RNA制御 / 精子形成
Outline of Final Research Achievements

In the germ cell development, regulatory mechanisms mediated via the function of RNA binding proteins are especially important. We have focused on functions of Nanos2 and Nanos3, which are expressed specifically in germ cells. We found that Nanos3 functions in the amplification process of undifferentiated spermatogonia during spermatogenesis, in addition to the important function in PGC development. On the other hand, Nanos2 suppresses expression of the target gene Dazl through binding to its 3'-UTR in the embryonic male germ cells. In addition, we found that Nanos2 maintains spermatogonial stem cell state via 1) direct recruitment and translational repression of genes that promote spermatogonial differentiation, and 2) repression of the target of rapamycin complex 1 (mTORC1), by sequestration of the core factor mTOR in mRNPs. This mechanism establishes a post-transcriptional buffering system to facilitate SSC homeostasis in the fluctuating environment within the seminiferous tubule.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(34 results)

All 2017 2016 2015 2014

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 5 results,  Acknowledgement Compliant: 8 results) Presentation (23 results) (of which Int'l Joint Research: 13 results,  Invited: 7 results)

  • [Journal Article] Roles of MIWI, MILI and PLD6 in small RNA regulation in mouse growing oocytes.2017

    • Author(s)
      Kabayama Y, Toh H, Katanaya A, Sakurai T, Chuma S, Kuramochi-Miyagawa S, Saga Y, Nakano T, Sasaki
    • Journal Title

      Nucleic acids research

      Volume: 印刷中 Pages: 5387-5398

    • DOI

      10.1093/nar/gkx027

    • NAID

      120006355769

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gonocytes-to-spermatogonia transition initiates prior to birth in murine testes and it requires FGF signaling.2017

    • Author(s)
      Pui HP, Saga Y.
    • Journal Title

      Mech Dev

      Volume: 印刷中 Pages: 125-139

    • DOI

      10.1016/j.mod.2017.03.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sexual Fate Change of XX Germ Cells Caused by the Deletion of SMAD4 and STRA8 Independent of Somatic Sex Reprogramming.2016

    • Author(s)
      Wu Q, Fukuda K, Kato Y, Zhou Z, Deng CX, Saga Y
    • Journal Title

      Plos biology

      Volume: 14(9)

    • DOI

      10.1371/journal.pbio.1002553

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Dead end1 is an essential partner of NANOS2 for selective binding of target RNAs in male germ cell development.2016

    • Author(s)
      Suzuki A, Niimi Y, Shinmyozu K, Zhou Z, Kiso M, Saga Y.
    • Journal Title

      EMBO Rep

      Volume: 17(1) Pages: 37-46

    • DOI

      10.15252/embr.201540828

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dazl is a target RNA suppressed by mammalian NANOS2 in sexually differentiating male germ cells2016

    • Author(s)
      Yuzuru Kato, Takeo Katsuki, Hiroki Kokubo, Aki Masuda, Yumiko Saga
    • Journal Title

      Nat Commun.

      Volume: 7 Pages: 1-11

    • DOI

      10.1038/ncomms11272

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The RNA binding protein Nanos2 organizes a post-transcriptional buffering system to retain primitive state of mouse spermatogonial stem cells.2015

    • Author(s)
      Zhi Zhou, Takayuki Shirakawa, Kazuyuki Ohbo, Aiko Sada, Quan Wu, Kazuteru Hasegawa, Rie Saba, Yumiko Saga
    • Journal Title

      Dev Cell

      Volume: 34 Pages: 96-107

    • DOI

      10.1016/j.devcel.2015.05.014

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells.2015

    • Author(s)
      Suzuki A, Niimi Y, Saga Y.
    • Journal Title

      Biology Open

      Volume: 3 Pages: 1164-1170

    • DOI

      10.1242/bio.20149308

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] TALEN-Mediated Gene Disruption on Y Chromosome Reveals Critical Role of EIF2S3Y in Mouse Spermatogenesis2015

    • Author(s)
      Matsubara Yohei, Kato Tomoko, Kashimada Kenichi, Tanaka Hiromitsu, Zhi Zhou, Ichinose Shizuko, Mizutani Shuki, Morio Tomohiro, Chiba Tomoki, Ito Yoshiaki, Saga Yumiko, Takada Shuji, and Asahara Hiroshi
    • Journal Title

      Stem Cells Dev

      Volume: 24 Pages: 1164-1170

    • DOI

      10.1089/scd.2014.0466

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SMAD2 and p38 signaling pathways act in concert to determine XY primordial germ cell fate in mice.2015

    • Author(s)
      Wu Q, Fukuda K, Weinstein M, Graff JM, Saga Y.
    • Journal Title

      Development

      Volume: 142 Pages: 575-586

    • DOI

      10.1242/dev.119446

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] CYP26B1 promotes male germ cell differentiation by suppressing STRA8-dependent meiotic and STRA8-independent mitotic pathways2014

    • Author(s)
      Saba R, Wu Q, Saga Y
    • Journal Title

      Dev Biol.

      Volume: 389 Pages: 173-181

    • DOI

      10.1016/j.ydbio.2014.02.013

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FGF8-FGFR1 signaling acts as a niche factor for maintaining undifferentiated spermatogonia in the mouse.2014

    • Author(s)
      Hasegawa K, Saga Y.
    • Journal Title

      Biol Reprod.

      Volume: 91 Pages: 145-145

    • DOI

      10.1095/biolreprod.114.121012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Germ cell-specific conditional KO via Cas9-mediated chimera analyses2017

    • Author(s)
      Yumiko Saga
    • Organizer
      The 20th US-Japan Cellular and Gene Therapy Conference
    • Place of Presentation
      FDA White Oak Campus, Maryland, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Egg or sperm: which is the default?2016

    • Author(s)
      Yumiko Saga,
    • Organizer
      The Allied Genetics Conference
    • Place of Presentation
      Orland, Florida, USA
    • Year and Date
      2016-07-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of a 3’UTR-dependent DAZL suppression in mouse postnatal ovary.2016

    • Author(s)
      Kurumi Fukuda, Yumiko Saga,
    • Organizer
      Mouse molecular genetics, The Allied Genetics Conference sponsored by the Genetics Society of America (GSA)
    • Place of Presentation
      Orland, Florida, USA
    • Year and Date
      2016-07-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sex determination of mouse germ cells.2016

    • Author(s)
      Yumiko Saga
    • Organizer
      International Symposium on Epigenetic Dynamics and Regulation in Germ Cells.
    • Place of Presentation
      kyoto
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Functional analyses of Nanos3 in mouse spermatogenesis.2016

    • Author(s)
      Takayuki Sakurai, Yumiko Saga.
    • Organizer
      International Symposium on Epigenetic Dynamics and Regulation in Germ Cells.
    • Place of Presentation
      Kyoto,
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intrinsic regulation of the timing of gonocytes-to spermatogonia transition in the murine testes by an RNA-binding Protein NANOS2.2016

    • Author(s)
      Han Pin Pui and Yumiko Saga.
    • Organizer
      International Symposium on Epigenetic Dynamics and Regulation in Germ Cells.
    • Place of Presentation
      Kyoto
    • Year and Date
      2016-02-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RNA制御を介した精子幹細胞の恒常性維持機構2016

    • Author(s)
      相賀裕美子、周智
    • Organizer
      日本分子生物学会
    • Place of Presentation
      横浜
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Role of post transcriptional suppression of Dazl via its 3’UTR in female reproduction2016

    • Author(s)
      Kurumi Fukuda, Yumiko Saga
    • Organizer
      日本発生生物学会Special Symposium
    • Place of Presentation
      Orland, Florida, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] An intrinsic buffering mechanism in spermatogonial stem cells controls the timing of mouse spermatogenesis.2015

    • Author(s)
      Yumiko Saga. Zhi Zhou.
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会(BMB2015).
    • Place of Presentation
      横浜
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Functional analyses of Nanos3 in mouse spermatogenesis.2015

    • Author(s)
      Takayuki Sakurai, Yumiko Saga.
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会(BMB2015)
    • Place of Presentation
      横浜
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウス卵形成における3'UTRを介したDazl発現抑制の役割2015

    • Author(s)
      福田胡桃、加藤譲、鈴木敦、相賀裕美子
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会(BMB2015)
    • Place of Presentation
      横浜
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Intrinsic regulation of the timing of gonocytes-to spermatogonia transition in the murine testes by an RNA-binding Protein NANOS2.2015

    • Author(s)
      Han Pin Pui and Yumiko Saga.
    • Organizer
      Mouse Molecular Genetics,
    • Place of Presentation
      Hinxton
    • Year and Date
      2015-09-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional analyses of Nanos3 in mouse spermatogenesis.2015

    • Author(s)
      Takayuki Sakurai, Yumiko Saga.
    • Organizer
      第47回発生生物学会
    • Place of Presentation
      つくば
    • Year and Date
      2015-05-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mechanism of Sex determination of mouse germ cells2015

    • Author(s)
      Yumiko Saga
    • Organizer
      Vertebrate Sex determination meeting
    • Place of Presentation
      Kona, Hawaii
    • Year and Date
      2015-04-17
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Sex determination of mouse germ cell2015

    • Author(s)
      Yumiko Saga
    • Organizer
      Finnish-Japanese joint symposium
    • Place of Presentation
      Helsinki
    • Year and Date
      2015-03-03
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Nanos2 antagonizes dazl to achieve sexual differentiation of male germ cells in mouse embryos2014

    • Author(s)
      Yuzuru Kato, Yumiko Saga.
    • Organizer
      CSH-GERM CELLS meeting
    • Place of Presentation
      NY
    • Year and Date
      2014-10-07
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mouse dead endi is an essential partner of NANOS2 for selective binding of target RNAS in male germ cell development.2014

    • Author(s)
      Atsushi Suzuki,Yuki Nimi, Kaori Shinmyouzu,Makoto Kiso, Yumiko Saga.
    • Organizer
      CSH-GERM CELLS meeting
    • Place of Presentation
      NY
    • Year and Date
      2014-10-07
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Female to male sex reversal of mouse PGCs independent of somatic environment.2014

    • Author(s)
      Quan Wu,Yumiko Saga.
    • Organizer
      CSH-GERM CELLS meeting
    • Place of Presentation
      NY
    • Year and Date
      2014-10-07
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nanos2 organizes a post-transcriptional buffering system in mouse Spermatogonia Stem Cells2014

    • Author(s)
      Zhou Zhi,Yumiko Saga
    • Organizer
      第47回発生生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] A revised model of gonocytes-to-spermatogonia transition in the mouse testis.2014

    • Author(s)
      Han Pin Pui,Yumiko Saga.
    • Organizer
      第47回発生生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Germ cell sexual differentiation requires Nanos2-mediated dosage control of Dazl in mice2014

    • Author(s)
      Yuzuru Kato,Yumiko Saga.
    • Organizer
      第47回発生生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Smad2 and p38 signaling orchestrate the male fate decision of mouse PGC.2014

    • Author(s)
      Quan Wu,Yumiko Saga.
    • Organizer
      第47回発生生物学会,
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Suppression of pluripofency gene together with NANOS2 is essential for male sexual differentiation in mouse germ cells.2014

    • Author(s)
      Hiroko Koike, Yumiko Saga.
    • Organizer
      第47回発生生物学会,
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-27
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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