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The role of Pax6 in spermatogenesis and determination of sex bias in the mouse

Research Project

Project/Area Number 17K19372
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biology of Cells to Organisms, and related fields
Research InstitutionTohoku University

Principal Investigator

Osumi Noriko  東北大学, 医学系研究科, 教授 (00220343)

Co-Investigator(Kenkyū-buntansha) 木村 龍一  東北大学, 医学系研究科, 助教 (00781759)
Research Collaborator Jasper Germeraad  
TATEHANA Misako  
Mai Lingling  
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
KeywordsPax6 / 精子形成 / 性比バイアス / 脳科学 / 基盤・社会脳科学 / 脳計測科学 / 性比 / 遺伝子 / 発生・分化 / 老化
Outline of Final Research Achievements

In this study, we examined whether the cause of biased sex ratio observed in spontaneous Pax6 mutant heterozygous (Sey/+) mice is in the process of spermatogenesis. Although the number of spermatogonia in the testis was similar between Sey/+ mice and wild-type littermates, the number of spermatocytes was significantly reduced in Sey/+ mice, suggesting that Pax6 dysfunction may affect the meiotic process. Furthermore, with fluorescent in situ hybridization for X and Y chromosomes, we also analyzed the proportion of sex chromosomes in round spermatids. Surprisingly, it became clear that the proportion of Y chromosome is significantly increased in round spermatids of Sey/+ mice. These results suggest that the biased sex ratio observed in Sey/+ mice may be due to the production of a large proportion of sperm having Y chromosome.

Academic Significance and Societal Importance of the Research Achievements

出生時の男女比は人種等に関わらずほぼ1.05対1であるが、その理由は不明であった。哺乳類の性は精子の性染色体によって決定され、減数分裂によりXおよびY染色体を持つ配偶子が同じ数だけ産生されるため、仔の性比は理論的には1:1となることが予想され、もし性バイアスが生じるのであれば、なんらかのメカニズムが必要となる。本研究は、減数分裂過程における転写制御因子・クロマチンリモデリング因子Pax6の機能不全が仔の性比に影響することを示した画期的な研究であり、今後その機構を明らかにすることで哺乳類の有する仔の性比調節において、精子形成の制御を介したエピジェネティックな機構が明らかになると期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (26 results)

All 2018 2017

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (18 results) (of which Int'l Joint Research: 1 results,  Invited: 14 results) Book (1 results)

  • [Journal Article] SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling2018

    • Author(s)
      Mochizuki Kentaro, Tando Yukio, Sekinaka Tamotsu, Otsuka Kei, Hayashi Yohei, Kobayashi Misato, Kamio Asuka, Ito-Matsuoka Yumi, Takehara Asuka, Kono Tomohiro, Osumi Noriko, Matsui Yasuhisa
    • Journal Title

      Development

      Volume: 145 Issue: 23 Pages: 1-10

    • DOI

      10.1242/dev.164160

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Repression of somatic genes by selective recruitment of HDAC3 by BLIMP1 is essential for mouse primordial germ cell fate determination2018

    • Author(s)
      Mochizuki Kentaro, Hayashi Yohei, Sekinaka Tamotsu, Otsuka Kei, Ito-Matsuoka Yumi, Kobayashi Misato, Oki Shinya, Takehara Asuka, Kono Tomohiro, Osumi Noriko, Matsui Yasuhisa
    • Journal Title

      Cell Reports

      Volume: 24 Issue: 10 Pages: 2682-2693

    • DOI

      10.1016/j.celrep.2018.07.108

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder2018

    • Author(s)
      Kikkawa Takako、Casingal Cristine R.、Chun Seung Hee、Shinohara Hiroshi、Hiraoka Kotaro、Osumi Noriko
    • Journal Title

      Brain Research

      Volume: - Pages: 30111-2

    • DOI

      10.1016/j.brainres.2018.02.041

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Induction of osteoblastic differentiation of neural crest-derived stem cells from hair follicles2017

    • Author(s)
      Urano-Morisawa Eri、Takami Masamichi、Suzawa Tetsuo、Matsumoto Akifumi、Osumi Noriko、Baba Kazuyoshi、Kamijo Ryutaro
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 4 Pages: e0174940-e0174940

    • DOI

      10.1371/journal.pone.0174940

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Polyunsaturated fatty acid deficiency during neurodevelopment in mice models the prodromal state of schizophrenia through epigenetic changes in nuclear receptor genes2017

    • Author(s)
      Maekawa M、Watanabe A、Iwayama Y、Kimura T、Hamazaki K、Balan S、Ohba H、Hisano Y、Nozaki Y、Ohnishi T、Toyoshima M、Shimamoto C、Iwamoto K、Bundo M、Osumi N、Takahashi E、Takashima A、Yoshikawa T
    • Journal Title

      Transl Psychiatry.

      Volume: 7 Issue: 9 Pages: e1229-e1229

    • DOI

      10.1038/tp.2017.182

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dab1 contributes differently to the morphogenesis of the hippocampal subdivisions2017

    • Author(s)
      Blume Marissa、Inoguchi Fuduki、Sugiyama Taku、Owada Yuji、Osumi Noriko、Aimi Yoshinari、Taki Kosuke、Katsuyama Yu
    • Journal Title

      Development, Growth & Differentiation

      Volume: 59 Issue: 8 Pages: 657-673

    • DOI

      10.1111/dgd.12393

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Early postnatal vocalizations predict sociability and spatial memory in C57BL6/J mice: individual differences in behavioral traits emerge early in development.2017

    • Author(s)
      Yoshizaki Kaichi, Koike Kohei, Kimura Ryuichi, Osumi Noriko
    • Journal Title

      PLoS One

      Volume: - Issue: 11 Pages: e0186798-e0186798

    • DOI

      10.1371/journal.pone.0186798

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 生物学総論2018

    • Author(s)
      Osumi, N.
    • Organizer
      REDEEM 平成30年度 第1回 出張講義
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Paternal aging affects gene expression of offspring’s brain possibly via epigenetic mechanism involving a transcriptional repressor REST2018

    • Author(s)
      Osumi, N.
    • Organizer
      国際神経発生生物学会第22回大会(ISDN2018)
    • Related Report
      2018 Annual Research Report
  • [Presentation] "An epigenetic model for neurodevelopmental disorders: paternal aging as an attributable risk"2018

    • Author(s)
      Osumi, N.
    • Organizer
      "45th IMSUT Founding Commemorative Symposium"
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Paternal Pax6 haploinsufficiency accelerated vocal communication deficits by advanced paternal aging2018

    • Author(s)
      Osumi, N.
    • Organizer
      CINP 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 父加齢の次世代行動への影響:進化に与える可能性についての考察2018

    • Author(s)
      大隅典子
    • Organizer
      日本進化学会第20回大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] "How paternal aging affects neural development of the offspring: an epigenetic model for neurodevelopment disorders"2018

    • Author(s)
      Osumi, N.
    • Organizer
      第40回日本生物学的精神医学会・第61回日本神経化学会大会 合同年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳からみた自閉症:ネズミを使った基礎研究2018

    • Author(s)
      大隅典子
    • Organizer
      市民のためのサイエンス講座2018「最新脳科学が解き明かす 脳とは何か?~脳を知って心を知る~」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Paternal aging induces atypical behaviors in offspring: a model for neurodevelopmental disorders and possible underlying mechanisms2018

    • Author(s)
      大隅典子
    • Organizer
      第18回「脳と心のメカニズム」冬のワークショップ
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 神経発達障害の謎に迫る:動物モデルからのアプローチ2018

    • Author(s)
      大隅典子
    • Organizer
      第11回ルートヴィッヒ・ボルツマンフォーラム2019年
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 文理共創パネルディスカッションA2018

    • Author(s)
      大隅典子
    • Organizer
      自閉症学(Autism Studies)シンポジウム2019
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 齧歯類を用いた音声コミュニケーション解析と遺伝的・環境的影響2017

    • Author(s)
      大隅典子
    • Organizer
      日本言語学会第154回大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] グリア系細胞における転写制御因子Pax6の機能2017

    • Author(s)
      大隅典子
    • Organizer
      新学術「グリアアセンブリによる脳機能発現の制御と病態」第4回夏のワークショップ
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 新学術「グリアアセンブリによる脳機能発現の制御と病態」第4回夏のワークショップ2017

    • Author(s)
      大隅典子
    • Organizer
      第32回日本下垂体研究会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Paternal aging affects offspring's behavior possibly via an epigenetic mechanism involving a transcriptional repressor REST2017

    • Author(s)
      Osumi, N.
    • Organizer
      Linkoping University-JSPS Meeting
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Effect of paternal aging on behavior of offspring in animal models of neurodevelopmental diseases2017

    • Author(s)
      Osumi, N.
    • Organizer
      第60回日本神経化学大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 父加齢の次世代マウス行動への影響に関わるエピゲノム機構2017

    • Author(s)
      大隅典子
    • Organizer
      第39回 日本生物学的精神医学会・第47回 日本神経精神薬理学会 合同年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Paternal aging-induced differential DNA methylation in sperm: possible effects on gene expression and behavior in offspring2017

    • Author(s)
      Osumi, N.Kimura R, Yoshizaki K, Koike T, Oki S, Mochizuki K, Kikkawa T, Inada H, Matsui Y, Kono T
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Paternal aging-induced differential DNA methylation in sperm: possible effects on gene expression and behavior in offspring2017

    • Author(s)
      Osumi, N.
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] 脳の誕生2017

    • Author(s)
      大隅 典子
    • Total Pages
      272
    • Publisher
      筑摩書房
    • ISBN
      9784480071019
    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-07-21   Modified: 2020-03-30  

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