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Gene-environmental interaction in early morphogenesis of the brain and developmental anomalies due to its disturbance

Research Project

Project/Area Number 19390050
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionKyoto University

Principal Investigator

SHIOTA Kohei  Kyoto University, 大学院・医学研究科, 名誉教授 (80109529)

Co-Investigator(Kenkyū-buntansha) ISHIBASHI Makoto  京都大学, 医学研究科, 教授 (30232341)
TAKIGAWA Toshiya  京都大学, 医学研究科, 助教 (90263095)
YAMADA Shigehito  京都大学, 医学研究科, 准教授 (80432384)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2009: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2008: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2007: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Keywords脳 / 形態形成 / 遺伝子 / 環境要因 / 発生異常 / 中枢系神経 / 外因 / エタノール / 全前脳胞症
Research Abstract

Sonic hedgehog (Shh) is a ventralizing factor in the developing brain. In this study, we showed that Shh is involved in the formation and patterning of the cerebral cortex and the morphogenesis of the ventral part of the eye. Ethanol exposure in early development can result in holoprosencephaly (HPE), which is a developmental anomaly of the forebrain. We used a mouse model of ethanol-induced HPE, and revealed that ethanol activates protein kinase C in the prechordal mesendoderm, thereby impairs the expression of Shh in the embryo and induces HPE malformations.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (26 results)

All 2010 2009 2008 2007 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (5 results) Book (2 results) Remarks (3 results)

  • [Journal Article] Early pathogenesis of holoprosencephaly.2010

    • Author(s)
      Shiota K, Yamada S
    • Journal Title

      Am J Med Genet Part C 154C

      Pages: 22-28

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sonic hedgehog is involved in formation of the ventral optic cup by limiting Bmp4 expression to the dorsal domain.2010

    • Author(s)
      Zhao L, Saitsu H, Sun X, Shiota K, Ishibashi M
    • Journal Title

      Mech Dev 127(1-2)

      Pages: 62-72

    • NAID

      120001887646

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sonic hedgehog is involved in formation of the ventral optic cup by limiting Bmp4 expression to the dorsal domain2010

    • Author(s)
      Zhao L, Saitsu H, Sun X, Shiota K, Ishibashi M
    • Journal Title

      Mechanisms of Development 127

      Pages: 62-72

    • NAID

      120001887646

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early pathogenesis of holoprosencephaly2010

    • Author(s)
      Shiota K, Yamada S
    • Journal Title

      American Journal of Medical Genetics Part C 154C

      Pages: 22-28

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of skull suture maintenance and interdigitation2009

    • Author(s)
      Miura T, Perlyn CA, Kinboshi M, Ogihara N, Kobayashi-Miura M, Morriss-Kay GM, Shiota K
    • Journal Title

      Journal of Anatomy 215

      Pages: 642-655

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hedgehog signaling is involved in development of the neocortex.2008

    • Author(s)
      Komada M, Saitsu H, Kinboshi M, Miura T, Shiota K, Ishibashi M
    • Journal Title

      Development 135

      Pages: 2717-2727

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Fgf15 is regulated by both activator and repressor forms of Gli2 in vitro.2008

    • Author(s)
      Komada M, Saitsu H, Shiota K, Ishibashi M
    • Journal Title

      Biochem Biophys Res Commun 369(2)

      Pages: 350-356

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fetal ethanol exposure activates protein kinase A and impairs Shh expression in prechordal mesendoderm cells in the pathogenesis of holoprosencephaly.2008

    • Author(s)
      Aoto K, Shikata Y, Higashiyama D, Shiota K, Motoyama J
    • Journal Title

      Birth Defects Res Part A 82(4)

      Pages: 224-231

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Fgf15 is regulated by both activator and repressor forms of Gli2 in vitro2008

    • Author(s)
      Komada M, Saitsu H, Shiota K, Ishibashi M
    • Journal Title

      Biochemical and Biophysical Research Communications 369

      Pages: 350-356

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hedgehog signaling is involved in development of the neocortex2008

    • Author(s)
      Komada M, Saitsu H, Kinboshi M, Shiota K, Ishibashi M
    • Journal Title

      Development 135

      Pages: 2717-2727

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fetal ethanol exposure activates protein kinase A and impairs Shh expression in prechordal mesendoderm cells in the pathogenesis of holoprosencephaly2008

    • Author(s)
      Aoto K, Shikata Y, Higashiyama D, Shiota K, Motoyama J
    • Journal Title

      Birth Defects Research Part A 82

      Pages: 224-231

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression dynamics of LIM-homeobox genes, Lhx1 and Lhx9, in the diencephalon during chick development2008

    • Author(s)
      Sun Xiangnan, Saitsu H, Shiota K, Ishibashi M
    • Journal Title

      Int J Dev Biol 52

      Pages: 33-41

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequential developmental changes in holoprosencephalic mouse embryos exposed to ethanol during the gastrulation period.2007

    • Author(s)
      Higashiyama D, Saitsu H, Komada M, Takigawa T, Ishibashi M, Shiota K
    • Journal Title

      Birth Defects Res A Clin Mol Teratol 79(7)

      Pages: 513-523

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Embryogenesis of holoprosencephaly.2007

    • Author(s)
      Shiota K, Yamada S, Komada M, Ishibashi M
    • Journal Title

      Am J Med Genet (Part A) 143A

      Pages: 3079-3087

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sequential developmental changes in holoprosencephalic mouseembryos exposed to ethanol during the gastrulation perio2007

    • Author(s)
      Higashiyama D, Saitsu H, Komada M, Takigawa T, Ishibashi M, Shiota K
    • Journal Title

      Birth Defects Res A Clin Mol Teratol 79(7)

      Pages: 513-523

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Embryogenesis of holoprosencephaly2007

    • Author(s)
      Shiota K, Yamada S, Komada M, Ishibashi M
    • Journal Title

      Am J Med Genet (Part A) 143A

      Pages: 3079-3087

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] The interplay of genetic and environmental factors in human dysmorphogenesis: Holoprosencephaly as a model.2009

    • Author(s)
      Shiota K
    • Organizer
      インドネシア解剖学会
    • Place of Presentation
      Jogjakarta, Indonesia. Shiota
    • Year and Date
      2009-08-07
    • Related Report
      2009 Final Research Report
  • [Presentation] The interplay of genetic and environmental factors in human dysmorphogenesis : Holoprosencephaly as a model2009

    • Author(s)
      塩田浩平
    • Organizer
      インドネシア解剖学会
    • Place of Presentation
      インドネシア ジョグジャカルタ市ガジャマダ大学
    • Year and Date
      2009-08-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] A digital atlas of human embryonic development using episcopic fluorescence image capture2008

    • Author(s)
      山田重人、Lee ES, Samtani RR, 上部千賀子、塩田浩平, ほか
    • Organizer
      第48回米国先天異常学会
    • Place of Presentation
      米国カリフォルニア州モントレー市
    • Year and Date
      2008-06-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] 先天異常の発生メカニズム一遺伝と環境の関わり2008

    • Author(s)
      塩田浩平
    • Organizer
      第48回日本先天異常学会
    • Place of Presentation
      東京都
    • Year and Date
      2008-06-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] Uwabe C: Holoprosencephaly in the Kyoto collection of human embryos: Phenotypic variability and epidemiologic characteristics.2007

    • Author(s)
      K, Yamada S
    • Organizer
      The 35th European Teratology Society Meeting
    • Place of Presentation
      Bratislava, Slovakia
    • Year and Date
      2007-09-03
    • Related Report
      2009 Final Research Report
  • [Book] FETAL NEUROLOGY2009

    • Author(s)
      Pooh RK, Kurjak A
    • Publisher
      Jaypee Brothers Medical Publishers
    • Related Report
      2009 Final Research Report
  • [Book] Controversies on the Beginning of Human Life2008

    • Author(s)
      Kurjak A, Chervenak FA
    • Publisher
      Jaypee Brothers Medical Publishers
    • Related Report
      2009 Final Research Report
  • [Remarks] (京都大学医学研究科先天異常標本解析センター)

    • URL

      http://www.cac.med.kyoto-u.ac.jp/

    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://www.cac.med.kyoto-u.ac.jp/

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.cac.med.kyoto-u.ac.jp/

    • Related Report
      2008 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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