The cell fate regulation mechanism during the development of neocortex controlled by the Hedgehog signaling.

• Project/Area Number: 24700353
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Aichi Gakuin University
• Principal Investigator: KOMADA Munekazu 愛知学院大学, 歯学部, 助教 (90523994)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 大脳皮質 / 神経発生 / 細胞周期 / ヘッジホッグシグナル / ドパミンニューロン / 大脳皮質形成 / 神経新生 / 細胞増殖 / 神経幹細胞 / 形態形成 / 神経分化

Research Abstract

The neocortex comprises several neuronal subtypes and neural glial cells. Differentiation of these cells is regulated by various factors during corticogenesis. In this study, to confirm the mechanism of corticogenesis controlled by the morphogen Hedgehog (HH) signaling, we established conditional knockout (cKO) mice in which the expression of Smo, an HH-signaling mediator, was inhibited in the dorsal telencephalon during development. HH signaling coordinates neurogenesis and cell cycle kinetics via its regulation of cyclin D2 expression. In Smo cKO mice, layer 6b exhibited hypoplasticity with decreased dopaminergic neuronal projections in the prefrontal cortex. These findings suggest that the histologic anomalies in the developing neocortex induced neuronal network abnormalities.

Research Products

• [Journal Article] Neurobehavioral evaluation of mouse newborns exposed prenatally to low-dose bisphenol A (2014)
  • Author(s): Tetsuji Nagao, Kota Kawachi, Nao Kagawa, Munekazu Komada,
  • Journal Title: The Journal of Toxicological Sciences Volume: 39 Issue: 2 Pages: 231-235
  • DOI: 10.2131/jts.39.231
  • NAID: 130004903983
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed
• [Journal Article] Smoothened controls cyclin D2 expression and regulates the generation of intermediate progenitors in the developing cortex (2013)
  • Author(s): Komada M, Iguchi T, Takeda T, Sato M.
  • Journal Title: Neuroscience Letter Volume: 28 Pages: 87-91
• [Journal Article] WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration (2013)
  • Author(s): Xie M, Yagi H, Kuroda K, Wang C, Komada M, Zhao H, Sakakibara A, Miyata T, Nagata K, Oka Y, Iguchi T, Sato M.
  • Journal Title: Cerebral Cortex Volume: 23 Pages: 1410-1423
• [Journal Article] Newly developed mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants (2013)
  • Author(s): Nagao T, Kagawa N, Komada M.
  • Journal Title: Journal of Applied Toxicology Volume: 33 Pages: 1514-1519
• [Journal Article] Smoothened controls cyclin D2 expression and regulates the generation of intermediate progenitors in the developing cortex. (2013)
  • Author(s): Munekazu Komada, Tokuichi Iguchi, Takehiko Takeda, Makoto Sato
  • Journal Title: Neurosci. Lett. Volume: 28(547) Pages: 87-91
  • Peer Reviewed
• [Journal Article] WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration (2013)
  • Author(s): Xie, M.-J., Yagi, H., Kuroda, K., Wang C.-C., Komada, M., Zhao, H., Sakakibara, A., Miyata, T., Nagata, K., Oka, Y., Iguchi, T. and Sato, M.
  • Journal Title: Cerebral Cortex Volume: (in press) Issue: 6 Pages: 1410-1423
  • DOI: 10.1093/cercor/bhs123
  • Peer Reviewed
• [Journal Article] Maternal bisphenol A oral dosing relates to the acceleration of neurogenesis in the developing neocortex of mouse fetuses (2012)
  • Author(s): Komada M., Asai Y., Morii M., Matsuki M., Sato M., Nagao T.
  • Journal Title: Toxicology Volume: 16 Pages: 325-330
• [Journal Article] Hedgehog signaling coordinates the proliferation and differentiation of neural stem/progenitor cells by regulating the cell cycle kinetics during development of the neocortex (2012)
  • Author(s): Komada M.
  • Journal Title: Congenital Anomalies Volume: 52 Pages: 72-77
• [Journal Article] Newly developed mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants (2012)
  • Author(s): Nagao T, Komada M, Kagawa N
  • Journal Title: J Appl Toxicol Volume: - Issue: 12 Pages: 1514-1519
  • DOI: 10.1002/jat.2802
  • Peer Reviewed
• [Journal Article] Developmental effects of oral exposure to diethylstilbestrol on mouse placenta. (2012)
  • Author(s): Nagao T., Kagawa N., Saito Y., Komada M.
  • Journal Title: Journal of Applied Toxicology Volume: -
  • Peer Reviewed
• [Journal Article] WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration (2012)
  • Author(s): Xie MJ., Yagi H., Kuroda K., Wang CC., Komada M., Zhao H., Sakakibara A., Miyata T., Nagata KI., Oka Y., Iguchi T., Sato M.
  • Journal Title: Cerebral Cortex Volume: -
  • Peer Reviewed
• [Journal Article] Hedgehog signaling coordinates the proliferation and differentiation of neural stem/progenitor cells by regulating the cell cycle kinetics during development of the neocortex (2012)
  • Author(s): Komada M.
  • Journal Title: Congenital Anomalies Volume: (in press) Issue: 2 Pages: 72-77
  • DOI: 10.1111/j.1741-4520.2012.00368.x
  • Peer Reviewed
• [Presentation] 大脳皮質形成におけるステロイドホルモンの役割 (2014)
  • Author(s): 駒田致和,池田やよい
  • Organizer: 第119回日本解剖学会学術大会・総会
  • Place of Presentation: 栃木
• [Presentation] 大脳皮質形成におけるステロイドホルモンの役割 (2014)
  • Author(s): 駒田致和，池田やよい
  • Organizer: 第119回日本解剖学会学術集会・総会
  • Place of Presentation: 自治医科大学キャンパス（栃木）
• [Presentation] 生後SF-1ノックアウトマウスPOAにおける脳の性分化マーカーの発現 (2013)
  • Author(s): 池田やよい,加藤朋子,駒田致和,加藤大貴,高橋幸子
  • Organizer: 第118回日本解剖学会学術集会・総会
  • Place of Presentation: 香川
  • Year and Date: 2013-03-28
• [Presentation] 大脳皮質形成におけるステロイドホルモンの局在と役割 (2013)
  • Author(s): 駒田致和,池田やよい
  • Organizer: 第55回日本歯科基礎医学会学術大会・総会
  • Place of Presentation: 岡山
• [Presentation] 化学物質胎児期曝露が誘発する新生児行動異常とその原因となる大脳皮質形態異常の解析 (2013)
  • Author(s): 駒田致和,長尾哲二
  • Organizer: 第53回日本先天異常学会学術集会・総会
  • Place of Presentation: 大阪
• [Presentation] DBZKOマウスにおける大脳皮質発達の解析 (2013)
  • Author(s): 服部剛志,岡本昌之,駒田致和,小山佳久,高雄啓三,宮川剛,片山泰一,伊藤彰,佐藤真,遠山正彌
  • Organizer: Neuro2013
  • Place of Presentation: 京都
• [Presentation] SF-1ノックアウトマウスPOAにおけるプロゲステロン受容体とkisspeptinの発現 (2013)
  • Author(s): 池田やよい,加藤朋子,加藤大貴,高橋幸子,駒田致和
  • Organizer: Neuro2013
  • Place of Presentation: 京都
• [Presentation] DBZKOマウスにおける大脳皮質発達の解析 (2013)
  • Author(s): 服部剛志，岡本昌之，駒田致和，小山佳久，高雄啓三，宮川剛，片山泰一，伊藤彰，佐藤真，遠山正彌
  • Organizer: Neuro2013
  • Place of Presentation: 京都国際会議場（京都）
• [Presentation] SF-1ノックアウトマウスのPOAにおけるプロゲステロン受容体とkisspeptinの発現 (2013)
  • Author(s): 池田やよい, 加藤朋子, 加藤大貴, 高橋幸子, 駒田致和
  • Organizer: Neuro2013
  • Place of Presentation: 京都国際会議場（京都）
• [Presentation] 化学物質胎児期曝露が誘発する新生児行動異常とその原因となる大脳皮質形態異常の解析 (2013)
  • Author(s): 駒田致和，長尾哲二
  • Organizer: 第53回日本先天異常学会学術集会・総会
  • Place of Presentation: 大阪千里ライフサイエンスセンター（大阪）
• [Presentation] 大脳皮質形成におけるステロイドホルモンの局在と役割 (2013)
  • Author(s): 駒田致和，池田やよい
  • Organizer: 第55回歯科基礎医学会学術大会・総会
  • Place of Presentation: 岡山コンベンションセンター（岡山）
• [Presentation] 生後SF-1ノックアウトマウスPOAにおける脳の性分化マーカーの発現 (2013)
  • Author(s): 池田やよい 加藤朋子 駒田致和 加藤大貴 高橋幸子
  • Organizer: 解剖学会
  • Place of Presentation: サンポートホール高松・かがわ国際会議場（香川）
• [Presentation] 胎児期4-ヒドロキシタモキシフェン曝露はマウス大脳皮質形成を障害する (2012)
  • Author(s): 溝端彩,森佳奈美,駒田致和,長尾哲二
  • Organizer: 第15回環境ホルモン学会研究発表会
  • Place of Presentation: 東京
  • Year and Date: 2012-12-02
• [Presentation] 低用量ビスフェノールAのマウス子宮内曝露は新生児の出生直後の活動量に影響を及ぼす (2012)
  • Author(s): 長尾哲二,井藤早紀,正見寛子,駒田致和
  • Organizer: 第15回環境ホルモン学会研究発表会
  • Place of Presentation: 東京
  • Year and Date: 2012-12-01
• [Presentation] ミトコンドリア由来のROSシグナルは骨芽細胞の分化を誘導する (2012)
  • Author(s): 駒田致和,新垣尚捷,山崎哲男
  • Organizer: 第51回日本薬学会中国四国支部
  • Place of Presentation: 島根
  • Year and Date: 2012-11-11
• [Presentation] 胎児期低用量ビスフェノールA曝露は大脳皮質形成において神経新生を促進する (2012)
  • Author(s): 駒田致和,浅井泰子,守井見奈,松木美知枝,佐藤真,長尾哲二
  • Organizer: 第52回日本先天異常学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-07-07
• [Presentation] 胎児期低用量ビスフェノールA曝露は大脳皮質形成において神経新生を促進する (2012)
  • Author(s): 駒田致和、浅井泰子 守井見奈 松木美知枝 佐藤真 長尾哲二
  • Organizer: 先天異常学会
  • Place of Presentation: 東京女子医科大学（東京都）
• [Presentation] ミトコンドリア由来のROSシグナルは骨芽細胞の分化を誘導する (2012)
  • Author(s): 駒田致和 新垣尚捷 山崎哲男
  • Organizer: 薬学会中国四国支部
  • Place of Presentation: 島根県民会館 サンラボーむらくも（島根県）
• [Presentation] 低用量ビスフェノールAのマウス子宮内曝露は新生児の出生直後の活動量に影響を及ぼす (2012)
  • Author(s): 長尾哲二 井藤早紀 正見寛子 駒田致和
  • Organizer: 環境ホルモン学会
  • Place of Presentation: 東京大学（東京都）
• [Presentation] 胎児期4-ヒドロキシタモキシフェン曝露はマウス大脳皮質形成を障害する (2012)
  • Author(s): 溝端彩 森佳奈美 駒田致和 長尾哲二
  • Organizer: 環境ホルモン学会
  • Place of Presentation: 東京大学（東京都）