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

• Project/Area Number: 19390050
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Kyoto 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: ¥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.

Research Products

• [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
  • 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
  • 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: Mechanisms of Development 127 Pages: 62-72
  • NAID: 120001887646
  • Peer Reviewed
• [Journal Article] Early pathogenesis of holoprosencephaly (2010)
  • Author(s): Shiota K, Yamada S
  • Journal Title: American Journal of Medical Genetics Part C 154C Pages: 22-28
  • Peer Reviewed
• [Journal Article] Mechanism of skull suture maintenance and interdigitation (2009)
  • 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
  • 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
  • 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
  • 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
  • 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: Biochemical and Biophysical Research Communications 369 Pages: 350-356
  • Peer Reviewed
• [Journal Article] Hedgehog signaling is involved in development of the neocortex (2008)
  • Author(s): Komada M, Saitsu H, Kinboshi M, Shiota K, Ishibashi M
  • Journal Title: Development 135 Pages: 2717-2727
  • 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 Research Part A 82 Pages: 224-231
  • Peer Reviewed
• [Journal Article] Expression dynamics of LIM-homeobox genes, Lhx1 and Lhx9, in the diencephalon during chick development (2008)
  • Author(s): Sun Xiangnan, Saitsu H, Shiota K, Ishibashi M
  • Journal Title: Int J Dev Biol 52 Pages: 33-41
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Sequential developmental changes in holoprosencephalic mouseembryos exposed to ethanol during the gastrulation perio (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
  • 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
  • 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
• [Presentation] The interplay of genetic and environmental factors in human dysmorphogenesis : Holoprosencephaly as a model (2009)
  • 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
• [Presentation] A digital atlas of human embryonic development using episcopic fluorescence image capture (2008)
  • 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
• [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
• [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
• [Book] FETAL NEUROLOGY (2009)
  • Author(s): Pooh RK, Kurjak A
  • Publisher: Jaypee Brothers Medical Publishers
• [Book] Controversies on the Beginning of Human Life (2008)
  • Author(s): Kurjak A, Chervenak FA
  • Publisher: Jaypee Brothers Medical Publishers
• [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/
• [Remarks]
  • URL: http://www.cac.med.kyoto-u.ac.jp/
• [Remarks]
  • URL: http://www.cac.med.kyoto-u.ac.jp/