メダカにおける脳神経新生を介した社会性行動発達に関する研究

• Project/Area Number: 13J08781
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Research Field: Computer system
• Research Institution: The University of Tokyo
• Principal Investigator: 磯江 泰子 東京大学, 理学系研究科, 特別研究員(DC1)
• Project Period (FY): 2013-04-26 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2015: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2014: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2013: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: 神経新生 / 終脳 / 細胞系譜 / 社会性行動 / 硬骨魚類 / メダカ / クローナルユニット / IR-LEGO

Outline of Annual Research Achievements

終脳は発生過程において神経管の最も先端の脳のふくらみから生じる、脊椎動物に共通した脳構造である。哺乳類では大脳に対応しており、高次中枢として機能する。終脳は神経管の背側から発生する「外套」と腹側から発生する「外套下部」に分けられ、両者は構造と機能が大きく異なる。「外套」は海馬や大脳皮質を含んでおり、内部が多くの区画化された解剖学的領域に分かれ、機能分化する。外套の構造と機能は種間で大きく異る。一方で「外套下部」は大脳基底核を含み、種間で比較的保存される。しかし胚発生過程において神経管から外套・外套下部が分化する分子機構は脊椎動物間で保存されるため成体における種差や区画化構造の構築原理は不明であった。そこで、成体の外套・外套下部の内部構造の構築や機能分化は生後の脳発達過程で生じるのではと考え、「生後の成長過程における終脳構築機構」に着目した研究に着手した。
モデル動物として硬骨魚類メダカを用いた。硬骨魚類では成長段階において脳全体で神経新生が生じ、神経細胞数が稚魚から成魚にかけて5～10倍程度増加するため、新生ニューロンが脳構造の構築に大きく寄与すると予想された。修士課程では遺伝子改変メダカを用いて神経新生を追跡し、幼魚及び成魚脳の新生ニューロンを可視化した。次に発生初期に少数の神経幹細胞に由来する細胞系譜を可視化した結果、成魚終脳の背側において区画構造が観察された。博士課程では、成長段階において同一の神経幹細胞由来の新生ニューロン群（細胞系譜単位）が終脳の区画化構造を構築するという仮説を立て、終脳全体における細胞系譜の体系的な解析を行なった。その結果、「外套」に対応する背側で区画化構造、脊椎動物「外套下部」に対応する腹側でモザイク構造をつくることを発見した。脊椎動物の大脳（終脳）構築様式を、発達期に生じる新生ニューロンの細胞系譜という観点から解明したのは本研究が初めてである。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Ontogeny and Sexual Differences in Swimming Proximity to Conspecifics in Response to Visual Cues in Medaka Fish. (2016)
  • Author(s): Yasuko Isoe, Yumi Konagaya, Saori Yokoi, Takeo Kubo, Hideaki Takeuchi
  • Journal Title: Zoological Science Volume: 33 Pages: 3-3
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A neural mechanism underlying mating preferences for familiar individuals in medaka fish. (2014)
  • Author(s): Okuyama T, Yokoi S, Abe H, Isoe Y, Suehiro Y, Imada H, Tanaka M, Kawasaki T, Yuba S, Taniguchi Y, Kamei Y, Okubo K, Shimada A, Naruse K, Takeda H, Oka Y, Kubo T, Takeuchi H
  • Journal Title: Science (New York, N.Y.) Volume: 343 Issue: 6166 Pages: 91-94
  • DOI: 10.1126/science.1244724
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Controlled Cre/loxP Site-Specific Recombination in the Developing Brain in Medaka Fish, Oryzias latipes (2013)
  • Author(s): Okuyama T, Isoe Y, Hoki M, Suehiro Y, Yamagishi G, Naruse K, Kinoshita M, Kamei Y, Shimizu A, Kubo T, Takeuchi H
  • Journal Title: PLOS one Volume: 8 Issue: 6 Pages: e66597-e66597
  • DOI: 10.1371/journal.pone.0066597
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Analysis of construction mechanism of medaka telencephalon by post-hatch neurogenesis (2016)
  • Author(s): Yasuko Isoe
  • Organizer: 9th Annual Meeting for Japanese Developmental Neuroscientists
  • Place of Presentation: 東京医科歯科大学（東京都・文京区）
  • Year and Date: 2016-03-19
• [Presentation] Behavioral development of conspecific interaction in Japanese medaka fish (Oryzias latipes). (2015)
  • Author(s): Isoe Yasuko, Konagaya Yumi, Yokoi Saori, Kubo Takeo, Takeuchi Hideaki
  • Organizer: Neuro2015/The 37th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2015-09-30
• [Presentation] Clonal Analysis of Newborn Neurons in the Telencephalon of Medaka Fish (2015)
  • Author(s): Yasuko Isoe, Teruhiro Okuyama, Masahito Hoki, Yuji Suehiro, Genki Yamagishi,Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Shigenori Nonaka, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: 21st Japanese Medaka and Zebrafish Meeting
  • Place of Presentation: 大阪大学（大阪府・大阪市）
  • Year and Date: 2015-09-19
• [Presentation] Analysis of mechanism underlying brain growth accompanied by neurogenesis using medaka fish (Oryzias latipes) (2014)
  • Author(s): Yasuko Isoe, Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: Neuroscience 2014/SfN
  • Place of Presentation: ワシントン（アメリカ）
  • Year and Date: 2014-11-17
  • Int'l Joint Research
• [Presentation] Clonal analysis of young neurons in telencephalon by using Japanese small fish, medaka fish (2014)
  • Author(s): Yasuko Isoe, Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: Massachusetts General Hospital & The University of Tokyo Joint Symposium 2014 "Frontiers in Biomedical Engineering"
  • Place of Presentation: ボストン（アメリカ）
  • Year and Date: 2014-09-24
  • Int'l Joint Research
• [Presentation] Analysis of mechanism underlying brain growth accompanied by neurogenesis using medaka fish (Oryzias latipes). (2014)
  • Author(s): Yasuko Isoe, Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: Neuro2014/The 36th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜）
  • Year and Date: 2014-09-12
• [Presentation] Analysis of mechanism underlying brain growth accompanied by neurogenesis using medaka fish (Oryzias latipes). (2014)
  • Author(s): Yasuko Isoe, Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: IGER International Symposium on Neural Circuits
  • Place of Presentation: 名古屋大学（愛知県・名古屋）
  • Year and Date: 2014-09-09
• [Presentation] Analysis of mechanism underlying brain growth accompanied by neurogenesis using medaka fish (Oryzias latipes). (2014)
  • Author(s): Yasuko Isoe, Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: 2014 International Congress of Neuroethology/The Japanese Society for comparative Physiology and Biochemistry
  • Place of Presentation: 北海道大学（北海道・札幌）
  • Year and Date: 2014-07-29
  • Int'l Joint Research
• [Presentation] Analysis of mechanism underlying brain growth accompanied by neurogenesis using medaka fish (Oryzias latipes) (2014)
  • Author(s): Yasuko Isoe, Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: Strategical meeting for medaka research
  • Place of Presentation: セビリア（スペイン）
  • Year and Date: 2014-04-11
  • Int'l Joint Research
• [Presentation] IR-LEGOを用いた、メダカ終脳の神経新生領域の区画化の解析 (2014)
  • Author(s): Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: 若手研究者による分野間連携研究プロジェクト
  • Place of Presentation: 三鷹
  • Year and Date: 2014-03-24
• [Presentation] Analysis of mechanism underlying brain growth accompanied by neurogenesis using medaka fish (Oryzias latipes), (2013)
  • Author(s): Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 京都
  • Year and Date: 2013-12-03
• [Presentation] A heat-inducible cre/loxp recombination in the brain of medaka fish (Oryzias latipes) (2013)
  • Author(s): Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: Neuroscience 2013/ SfN
  • Place of Presentation: アメリカ・サンディエゴ
  • Year and Date: 2013-11-12
• [Presentation] Analysis of mechanism underlying brain growth accompanied by neurogenesis using medaka fish (Oryzias latipes) (2013)
  • Author(s): Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: 19th Japanese Medaka and Zebrafish Meeting
  • Place of Presentation: 仙台
  • Year and Date: 2013-09-20
• [Presentation] Analysis of mechanism underlying brain growth accompanied by neurogenesis using medaka fish (Oryzias latipes) (2013)
  • Author(s): Teruhiro Okuyama,Masahito Hoki, Yuji Suehiro, Genki Yamagishi, Kiyoshi Naruse, Masato Kinoshita, Yasuhiro Kamei, Atushi Shimizu, Takeo Kubo, Hideaki Takeuchi
  • Organizer: Neuro2013 / The 36th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 神戸
  • Year and Date: 2013-06-20