Angiogenic mechanism spatio-temporally controlled by Id-Notch signal crosstalk and their therapeutic application

• Project/Area Number: 23591099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: NISHIYAMA Koichi 東京大学, 医学(系)研究科(研究院), 助教 (80398221)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 発生・分化 / 血管新生 / ライブイメージング / 転写因子 / 多細胞運動 / モデル化

Research Abstract

This study aimed to examine whether or not or how a signal crosstalk between HLH transcriptional factor Id and Notch contributes to the spatio-temporal control of endothelial cell behaviors during angiogenesis. A 4D analysis using an in vitro angiogenesis model suggested that the crosstalk possibly related to the dynamic regulation of moving speed and direction in individual endothelial cells. However, "cell sorting" phenomenon did not seem to explain the regulatory mechanism. Furthermore, we constructed a mathematical model for endothelial cell dynamics driving VEGF-induced vessel elongation, which enables us to further dissect the mechanisms systemically.

Research Products

• [Journal Article] Endothelin regulates neural crest deployment and fate to form great vessels through D1x5/D1x6-independent mechanisms. (2013)
  • Author(s): Kim KS, Arima Y, Kitazawa T, Nishiyama K, Asai R, Uchijima Y, Sato T, Levi G, Kitanaka S, Igarashi T, Kurihara Y, Kurihara H.
  • Journal Title: Mechanism of Development Volume: 130 Issue: 11-12 Pages: 553-566
  • DOI: 10.1016/j.mod.2013.07.005
  • Peer Reviewed / Open Access
• [Journal Article] Resistin-Like Molecule β Is Abundantly Expressed in Foam Cells and Is Involved in Atherosclerosis Development. (2013)
  • Author(s): Kushiyama A, Sakoda H, Oue N, Okubo M, Nakatsu Y, Ono H, Fukushima T, Kamata H, Nishimura F, Kikuchi T, Fujishiro M, Nishiyama K, Aburatani H, Kushiyama S, Iizuka M, Taki N, Encinas J, Sentani K, Ogonuki N, Ogura A, Kawazu S, Yasui W, Higashi Y, Kurihara H, Katagiri H, Asano T.
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 33 Issue: 8 Pages: 1986-1993
  • DOI: 10.1161/atvbaha.113.301546
  • Peer Reviewed / Open Access
• [Journal Article] in vitroライブイメージングと定量解析による血管新生機構の解明 (2013)
  • Author(s): 西山功一
  • Journal Title: 日本血栓止血学会誌 Volume: 24(6) Pages: 553-559
  • NAID: 130003393317
• [Journal Article] Preotic neural crest cells contribute to coronary smooth muscle involving endothelin signalling. (2012)
  • Author(s): Yuichiro Arima
  • Journal Title: Nature Communications Volume: 3 Issue: 1 Pages: 1267-1267
  • DOI: 10.1038/ncomms2258
  • Peer Reviewed
• [Journal Article] Angiogenic morphogenesis driven by dynamic and heterogeneous collective endothelial cell movement (2011)
  • Author(s): Arima S, Nishiyama K, Ko T, Arima Y, Hakozaki Y, Sugihara K, Koseki H, Uchijima Y, Kurihara Y, Kurihara H.
  • Journal Title: Development Volume: 138 Issue: 21 Pages: 4763-4776
  • DOI: 10.1242/dev.068023
  • Peer Reviewed
• [Journal Article] Identification and developmental analysis of endothelin receptor type-A expressing cells in the mouse kidney (2011)
  • Author(s): Kitazawa T, Sato T, Nishiyama K, Asai R, Arima Y, Uchijima Y, Kurihara Y, Kurihara H.
  • Journal Title: Gene Expr. Patterns Volume: 11 Issue: 7 Pages: 371-377
  • DOI: 10.1016/j.gep.2011.04.001
  • Peer Reviewed
• [Journal Article] Calpain-6, a microtubule-stabilizing protein, regulates Rac1 activity and cell motility through interaction with GEF-H1 (2011)
  • Author(s): Kazuo Tonami
  • Journal Title: Journal of Cell Science Volume: 124巻 Issue: 8 Pages: 1214-1223
  • DOI: 10.1242/jcs.072561
  • Peer Reviewed
• [Journal Article] Angiogenic morphogenesis driven by dynamic and heterogeneous collective endothelial movement (2011)
  • Author(s): Satoshi Arima, Koichi Nishiyama
  • Journal Title: Development Volume: 138(21) Pages: 4763-4776
  • Peer Reviewed
• [Journal Article] Calpain-6, a microtubule-stabilizing protein, regulates Rac1 activity and cell motility through interaction with GEF-H1 (2011)
  • Author(s): Kazuo Tonami
  • Journal Title: J Cell Sci Volume: 124(Pt8) Pages: 1214-1223
  • Peer Reviewed
• [Presentation] 血管新生における血管内皮細胞運動の制御系としての壁細胞の役割 (2013)
  • Author(s): 西山功一
  • Organizer: 第21回日本血管生物医学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2013-09-06
• [Presentation] かたちをつくる血管細胞動態と数理モデル化 (2013)
  • Author(s): 西山功一
  • Organizer: 「非線形離散可積分系の新展開」RIMS研究集会
  • Place of Presentation: 京都
  • Year and Date: 2013-09-02
• [Presentation] Angiogenic morphogenesis : analyses of the self-organizing mechanisms of vascular cells using"imaging and modeling" (2013)
  • Author(s): Nishiyama K
  • Organizer: The 11^<th> Japan-Korea Joint Symposium on Vascular Biology
  • Place of Presentation: Jeju
  • Year and Date: 2013-08-24
• [Presentation] Mural cells modulate collective endothelial cell movements to promote proper angiogenic morphogenesis (2013)
  • Author(s): Nishiyama K
  • Organizer: The Angiogenesis Gordon Research Conference
  • Place of Presentation: Newport
  • Year and Date: 2013-08-08
• [Presentation] 血管のかたちをつくる血管細胞動態の理解 (2013)
  • Author(s): 西山功一
  • Organizer: 第42回日本心脈管作動物質学会
  • Place of Presentation: 奈良
  • Year and Date: 2013-02-09
• [Presentation] Mural cells modulate collective endothelial cell movements to promote proper angiogenic morphogenesis (2013)
  • Author(s): Nishiyama K
  • Organizer: The Angiogenesis Gordon Research Conference
  • Place of Presentation: サルブ・レジーナ大学（米国）
• [Presentation] Cell-based mechanism behind angiogenic morphogenesis (2013)
  • Author(s): Koichi Nishiyama
  • Organizer: The 23rd CDB meeting
  • Place of Presentation: 理化学研究所 発生再生科学総合研究センター （兵庫県 神戸市）
• [Presentation] 血管のかたちをつくる血管細胞動態の理解 (2013)
  • Author(s): 西山 功一
  • Organizer: 第42回日本心脈管作動物質学会
  • Place of Presentation: 奈良県立新公会堂 （奈良県 奈良市）
  • Invited
• [Presentation] A novel mathematical model of endothelial cell dynamics during angiogenic morphogenesis : analysis of cell-based mechanism (2012)
  • Author(s): Sugihara K
  • Organizer: 第35回分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-11
• [Presentation] Imaging, quantification and modeling of self-organizing behaviors of vascular cells (2012)
  • Author(s): 西山功一
  • Organizer: 第20回日本血管生物医学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2012-12-06
• [Presentation] Cell-based mechanism behind angiogenic morphogenesis : analysis using both experimental and computational approaches (2012)
  • Author(s): Nishiyama K
  • Organizer: 7^<th> Kloster Seeon'Angiogenesis': Molecular Mechanism and Functional Interactions
  • Place of Presentation: Seeon
  • Year and Date: 2012-09-15
• [Presentation] 血管新生の形づくりを担う内皮細胞動態 (2012)
  • Author(s): 西山功一
  • Organizer: 第22回数理生物学会大会
  • Place of Presentation: 岡山
  • Year and Date: 2012-09-12
• [Presentation] 血管構造をつくる血管内皮細胞動態の可視化と理解 (2012)
  • Author(s): 西山功一
  • Organizer: 第34回日本血栓止血学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-06-09
• [Presentation] Analysis of cell-based mechanism involved in angiogenic morphogenesis by biological and computational approaches (2012)
  • Author(s): Nishiyama K
  • Organizer: The 17^<th> International Vascular Biology Meeting (IVBM) 2012
  • Place of Presentation: Wiesbaden
  • Year and Date: 2012-06-02
• [Presentation] A novel mathematical model of angiogenic morphogenesis : importance of tip cell dynamics (2012)
  • Author(s): Sugihara K
  • Organizer: 第46発生生物学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2012-05-30
• [Presentation] Ex vivo血管新生における血管内皮細胞の集団的運動 (2012)
  • Author(s): 西山功一
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 甲府
  • Year and Date: 2012-03-26
• [Presentation] A novel mathematical model of angiogenic morphogenesis: implication of tip cell dynamics (2012)
  • Author(s): Kei Sugihara
  • Organizer: 第46回発生生物学会大会
  • Place of Presentation: 神戸国際会議場 （兵庫県 神戸市）
• [Presentation] Analysis of cell-based mechanisms involved in angiogenic morphogenesis by biological and computational approaches (2012)
  • Author(s): Koichi Nishiyama
  • Organizer: 17th International Vascular Biology Meeting 2012
  • Place of Presentation: Rhein-Main-Hallen Wiesbaden （Germany Wiesbaden）
• [Presentation] 血管構造をつくる血管内皮細胞動態の可視化と理解 (2012)
  • Author(s): 西山 功一
  • Organizer: 第34回日本血栓止血学会学術集会
  • Place of Presentation: ハイアットリージェンシー東京 （東京都 千代田区）
  • Invited
• [Presentation] 血管の形づくりを担う内皮細胞動態 (2012)
  • Author(s): 西山 功一
  • Organizer: 第22数理生物学会大会
  • Place of Presentation: 岡山大学津島キャンパス （岡山県 岡山市）
  • Invited
• [Presentation] Cell-based mechanism behind angiogenic morphogenesis: analysis using both experimental and computational approaches (2012)
  • Author(s): Koichi Nishiyama
  • Organizer: 7th Kloster Seeon ‘Angiogenesis’: Molecular Mechanism and Functional Interactions
  • Place of Presentation: KLOSTER SEEON （Germany Seeon）
• [Presentation] Experimental and computational analysis underscores the importance of tip cell dynamics in angiogenic morphogenesis (2012)
  • Author(s): Koichi Nishiyama
  • Organizer: 第16回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京大学本郷キャンパス （東京都 文京区）
• [Presentation] Imaging, quantification and modeling of self-organizing behaviors of vascular cells (2012)
  • Author(s): Koichi Nishiyama
  • Organizer: 第20回日本血管生物医学会学術集会
  • Place of Presentation: あわぎんホール （徳島県 徳島市）
  • Invited
• [Presentation] A novel mathematical model of endothelial cell dynamics during angiogenic morphogenesis: analysis of cell-based mechanisms (2012)
  • Author(s): Kei Sugihara
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場 （福岡県 福岡市）
• [Presentation] Ex vivo血管新生における血管内皮細胞の集団的運動 (2012)
  • Author(s): Koichi Nishiyama
  • Organizer: 第117回日本解剖学会総会・全国学術集会(招待講演)
  • Place of Presentation: 山梨大学 （山梨県 甲府市
• [Presentation] Angiogenic morphogenesis driven by collective endothelial cell behavior (2011)
  • Author(s): Nishiyama K
  • Organizer: 第34回分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-13
• [Presentation] Mechanism involving dynamic and heterogeneous endothelial cell movement during angiogenesis (2011)
  • Author(s): Nishiyama K
  • Organizer: 第19回日本血管生物医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-12-09
• [Presentation] Morphogenetic cell mo vement in sprouting angiogenesis (2011)
  • Author(s): Nishiyama K
  • Organizer: 日蘭二国間交流セミナー
  • Place of Presentation: 東京
  • Year and Date: 2011-11-04
• [Presentation] Dynamic and Heterogeneous collective endothelial cell movement driving angiogenic morphogenesis (2011)
  • Author(s): Nishiyama K
  • Organizer: The Second Pacific Symposium on Vascular Biology
  • Place of Presentation: Jeju
  • Year and Date: 2011-10-31
• [Presentation] Id1 modulates sprouting angiogenesis possibly via spatiotemporal regulation of the Notch signal specification (2011)
  • Author(s): Nishiyama K
  • Organizer: 第84回日本生化学大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] Collective endothelial cell movement in angiogenic morphogenesis (2011)
  • Author(s): Nishiyama K
  • Organizer: The 9^<th> Japan-Korea Joint Symposium on vascular biology
  • Place of Presentation: Pusan
  • Year and Date: 2011-08-25
• [Presentation] Id1 may spatiotempora lly regulate endothelial cell moveme nts driving angiogenesis (2011)
  • Author(s): Nishiyama K
  • Organizer: AHA scie ntific session 2011
  • Place of Presentation: Orland
  • Year and Date: 2011-01-05
• [Presentation] Collective endothelial cell movement in angiogenic morphogenesis (2011)
  • Author(s): Koichi Nishiyama
  • Organizer: The 9th Japan-Korea Joint Symposium on vascular biology(招待講演)
  • Place of Presentation: ウエスティン朝鮮ホテル釜山(韓国)
• [Presentation] Id1 modulates sprouting angiogenesis possibly via spatiotemporal regulation of the Notch signal specification (2011)
  • Author(s): Koichi Nishiyama
  • Organizer: 第84回日本生化学大会
  • Place of Presentation: 国立京都国際会館 (京都府 京都市)
• [Presentation] Ex vivoにおける定量的血管新生評価系の開発 (2011)
  • Author(s): 西山 功一
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 栃木県総合文化センター （栃木県 宇都宮市）
• [Presentation] Dynamic and Heterogeneous collective endothelial cell movement driving angiogenic morphogenesis (2011)
  • Author(s): Koichi Nishiyama
  • Organizer: The Second Pacific Symposium on Vascular Biology
  • Place of Presentation: 済州新羅ホテル（韓国）
• [Presentation] Morphogenetic cell movement in sprouting angiogenesis (2011)
  • Author(s): Koichi Nishiyama
  • Organizer: 日蘭二国間交流セミナー(招待講演)
  • Place of Presentation: 昭和薬科大学（東京都 町田市）
• [Presentation] Id1 may spatiotemporally regulate endothelial cell movements driving angiogenesis (2011)
  • Author(s): Koichi Nishiyama
  • Organizer: American Heart Association Scientific Session
  • Place of Presentation: オーランドコンベンションセンター（米国）
• [Presentation] Mechanism involving dynamic and heterogeneous endothelial cell movement during angiogenesis (2011)
  • Author(s): Koichi Nishiyama
  • Organizer: 第19回日本血管生物医学会学術集会(招待講演)
  • Place of Presentation: 東京ステーションコンファレンス （東京都 千代田区）
• [Presentation] Angiogenic morphogenesis driven by collective endothelial cell behavior (2011)
  • Author(s): Koichi Nishiyama
  • Organizer: 第34回分子生物学会年会(招待講演)
  • Place of Presentation: 横浜パシフィコ（神奈川県 横浜市）
• [Presentation] Angiogenic morphogenesis: analyses of the self-organizing mechanisms of vascular cells using “imaging and modeling”
  • Author(s): Nishiyama K
  • Organizer: The 11th Japan-Korea Joint Symposium on Vascular Biology
  • Place of Presentation: ハイアットリージェンシー済州ホテル（韓国）
  • Invited
• [Presentation] かたちをつくる血管細胞動態と数理モデル化
  • Author(s): 西山功一
  • Organizer: 「非線形離散可積分系の新展開」RIMS研究集会
  • Place of Presentation: 京都大学（京都）
  • Invited
• [Presentation] Understanding of collective endothelial cell behaviors driving angiogenic morphogenesis using mathematical modeling
  • Author(s): Nishiyama K
  • Organizer: The 4th Molecular Cardiovascular Conference II
  • Place of Presentation: キロロリゾートホテルピアノ（余市）
• [Presentation] 血管新生における血管内皮細胞運動の制御系としての壁細胞の役割
  • Author(s): 西山功一
  • Organizer: 第21回日本血管生物医学会学術集会
  • Place of Presentation: 千里阪急ホテル（大阪府）
  • Invited
• [Presentation] 内皮細胞の自発的パターン形成 ～ブレークスルーを生むコラボレーション～
  • Author(s): 西山功一、三浦岳
  • Organizer: 日本発生生物学会 秋季シンポジウム2013
  • Place of Presentation: しあわせの村、野外活動センターあおぞら（神戸市）
  • Invited
• [Presentation] Modeling collective endothelial cell movement behind angiogenic morphogenesis
  • Author(s): Sugihara K
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Invited
• [Book] in vitroライブイメージングと定量解析による血管新生機構の解明、24(6) (2013)
  • Author(s): 西山功一
  • Publisher: 日本血栓止血学会誌
• [Book] 血管生物医学事典(NO、NOS、) (2011)
  • Author(s): 西山功一
  • Publisher: 朝倉書店
• [Book] 血管生物医学事典(Id) (2011)
  • Author(s): 西山功一
  • Publisher: 朝倉書店
• [Remarks]
  • URL: http://bio.m.u-tokyo.ac.jp/home-j.html
• [Remarks] 東京大学大学院医学系研究科代謝生理化学教室ホームページ
  • URL: http://bio.m.u-tokyo.ac.jp/home-j.html
• [Remarks]
  • URL: http://bio.m.u-tokyo.ac.jp/home-j.html