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Signaling pathways that regulate cardiovascular development and morphogenesis

Research Project

Project/Area Number 15H04883
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Nakagawa Osamu  国立研究開発法人国立循環器病研究センター, 研究所, 部長 (40283593)

Co-Investigator(Kenkyū-buntansha) 渡邉 裕介  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (20562333)
片山 由美  国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (20570675)
深山 俊治  国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (60779304)
瀬谷 大貴  国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (30806021)
田中 亨  国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (50806065)
西谷 友重  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (50393244)
久光 隆  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (50327946)
山岸 敬幸  慶應義塾大学, 医学部(信濃町), 教授 (40255500)
岩田 裕子  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (80171908)
坂部 正英  奈良県立医科大学, 医学部, 助教 (00525983)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords心血管系 / 発生 / 形態形成 / シグナル伝達 / 転写調節因子 / 先天性心疾患 / ノックアウトマウス / 発生・形態形成 / 心血管発生・形態形成 / 心血管発生
Outline of Final Research Achievements

Cardiovascular development and morphogenesis are controlled by a variety of cellular signaling pathways and gene regulatory systems, and their defects cause human congenital cardiovascular diseases. In this research project, we studied physiological significance of the genes that functioned as downstream targets of Notch and ALK1 signaling pathways by examining the abnormalities observed in the mouse models with gene deletions. In addition, we identified and characterized the enhancer regulatory regions for vascular endothelial expression of these genes. The information obtained in this project helps understand the molecular mechanisms of cardiovascular development and morphogenesis and the etiologies of congenital cardiovascular diseases.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (36 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (23 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Book (2 results) Remarks (2 results)

  • [Int'l Joint Research] Albert Einstein College of Medicine(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Serum/glucocorticoid-regulated kinase 1 as a novel transcriptional target of bone morphogenetic protein-ALK1 receptor signaling in vascular endothelial cells.2018

    • Author(s)
      Araki M, Hisamitsu T, Kinugasa-Katayama Y, Tanaka T, Harada Y, Nakao S, Hanada S, Ishii S, Fujita M, Kawamura T, Saito Y, Nishiyama K, Watanabe Y, Nakagawa O.
    • Journal Title

      Angiogenesis

      Volume: 21 Issue: 2 Pages: 415-423

    • DOI

      10.1007/s10456-018-9605-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of Collateral Source Characteristics With 3‐Dimensional Analysis Using Micro?X‐Ray Computed Tomography2018

    • Author(s)
      Arima Yuichiro、Hokimoto Seiji、Tabata Noriaki、Nakagawa Osamu、Oshima Asahi、Matsumoto Yosuke、Sato Takahiro、Mukunoki Toshifumi、Otani Jun、Ishii Masanobu、Uchikawa Michie、Yamamoto Eiichiro、Izumiya Yasuhiro、Kaikita Koichi、Ogawa Hisao、Nishiyama Koichi、Tsujita Kenichi
    • Journal Title

      Journal of the American Heart Association

      Volume: 7 Issue: 6

    • DOI

      10.1161/jaha.117.007800

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Placental labyrinth formation in mice requires endothelial FLRT2/UNC5B signaling2017

    • Author(s)
      Tai-Nagara Ikue、Yoshikawa Yusuke、Numata Naoko、Ando Tomofumi、Okabe Keisuke、Sugiura Yuki、Ieda Masaki、Takakura Nobuyuki、Nakagawa Osamu、Zhou Bin、Okabayashi Koji、Suematsu Makoto、Kitagawa Yuko、Bastmeyer Martin、Sato Kohji、Klein R?diger、Navankasattusas Sutip、Li Dean Y.、Yamagishi Satoru、Kubota Yoshiaki
    • Journal Title

      Development

      Volume: 144 Pages: 2392-2401

    • DOI

      10.1242/dev.149757

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Notch and Hippo signaling converge on Strawberry Notch 1 (Sbno1) to synergistically activate Cdx2 during specification of the trophectoderm.2017

    • Author(s)
      Watanabe Y, Miyasaka KY, Kubo A, Kida YS, Nakagawa O, Hirate Y, Sasaki H, Ogura T
    • Journal Title

      Scientific Reports

      Volume: 7:46135 Issue: 1 Pages: 46135-46135

    • DOI

      10.1038/srep46135

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Roles of endothelial Hrt genes for vascular development.2016

    • Author(s)
      Sakabe M, Morioka T, Kimura H, Nakagawa O.
    • Journal Title

      Etiology and morphogenesis of congenital heart disease

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TMEM100, a novel intracellular transmembrane protein essential for cardiovascular development.2016

    • Author(s)
      Mizuta K, Sakabe M, Somekawa S, Saito Y, Nakagawa O.
    • Journal Title

      Etiology and morphogenesis of congenital heart disease

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharyngeal arch artery defects and lethal malformations of the aortic arch and its branches in mice deficient for the Hrt1/Hey1 transcription factor.2016

    • Author(s)
      Fujita M, Sakabe M, Ioka T, Watanabe Y, Kinugasa-Katayama Y, Tsuchihashi T, Utset MF, Yamagishi H, Nakagawa O.
    • Journal Title

      Mechanisms of Development

      Volume: 139 Pages: 65-73

    • DOI

      10.1016/j.mod.2015.11.002

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 心血管形態形成におけるHrt/Hey転写調節因子の意義2015

    • Author(s)
      渡邉裕介、久光隆、片山由美、荒木睦、石井修平、藤田匡秀、坂部正英、中川修.
    • Journal Title

      循環器病研究の進歩

      Volume: 36 Pages: 74-82

    • Related Report
      2015 Annual Research Report
  • [Presentation] 咽頭弓に存在する二次心臓領域発生の分子機構2017

    • Author(s)
      渡邉裕介、中川 修
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Place of Presentation
      長崎
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Serum/glucocorticoid regulated kinase 1 as a novel transcriptional target of bone morphogenetic protein-ALK1 signaling in vascular endothelial cells2017

    • Author(s)
      Mutsumi ARAKI, Yusuke WATANABE, Takashi HISAMITSU, Yumi KINUGASA-KATAYAMA, Toru TANAKA, Yukihiro HARADA, Teruhisa KAWAMURA, Osamu NAKAGAWA
    • Organizer
      The 8th TAKAO International Symposium on Molecular Mechanism of Cardiopulmonary Disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Significance of Hey1 transcription factor in pharyngeal arch artery formation and regulatory mechanisms of its expression during embryonic development2017

    • Author(s)
      Yusuke WATANABE, Masahide FUJITA, Shuhei ISHII, Toshiharu FUKAYAMA, Dai IHARA, Daiki SEYA, Teruhisa KAWAMURA, Osamu NAKAGAWA
    • Organizer
      The 8th TAKAO International Symposium on Molecular Mechanism of Cardiopulmonary Disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BMP-ALK1シグナル伝達系の新しい下流遺伝子としてのSerum/glucocorticoid regulated kinase 1(SGK1)の意義2017

    • Author(s)
      荒木睦、渡邉裕介、久光隆、田中亨、原田恭弘、片山由美、川村晃久、中川修
    • Organizer
      第25回日本血管生物学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 胎生期血管内皮遺伝子Tmem100の心血管形成における発現制御機構2017

    • Author(s)
      片山由美、冨松彩佳、渡邉裕介、久光隆、瀬谷大貴、荒井勇二、磯本祥恵、斎藤義彦、中川修
    • Organizer
      第25回日本血管生物学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 咽頭弓に存在する二次心臓領域発生の分子機構2017

    • Author(s)
      渡邉裕介、中川修
    • Organizer
      第122回日本解剖学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Hey1 expression in pharyngeal arch and presomitic mesoderm is regulated by a distal enhancer2017

    • Author(s)
      渡邉裕介、石井修平、深山俊治、上本泰生、井原大、西谷友重、荒井勇二、中川修
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 胎生期血管内皮遺伝子Tmem100の心血管形態形成における発現制御機構の解析2017

    • Author(s)
      片山由美、冨松彩佳、渡邉裕介、久光隆、荒井勇二、磯本祥恵、斎藤義彦、中川修
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 胎生期血管内皮細胞におけるHey1遺伝子の発現制御機構2017

    • Author(s)
      深山俊治、渡邉裕介、瀬谷大貴、井原大、荒井勇二、磯本祥恵、中川修
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Hrt1/Hey1遺伝子の血管内皮発現制御機構におけるNotchおよびALK1シグナリングによる協調的転写調節メカニズム2016

    • Author(s)
      石井修平、渡邉裕介、上本泰生、井原大、久光隆、深山俊治、中川修
    • Organizer
      第20回日本心血管内分泌代謝学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-12-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Hrt1/Hey1遺伝子の血管内皮発現制御機構におけるNotchおよびALK1シグナリングによる協調的転写調節メカニズム2016

    • Author(s)
      渡邉裕介、石井修平、深山俊治、上本泰生、井原大、久光隆、荒井勇二、中川修
    • Organizer
      第24回日本血管生物医学会学術集会
    • Place of Presentation
      長崎
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胎生期血管内皮遺伝子TMEM100の心血管形態形成における発現制御機構の解析2016

    • Author(s)
      片山由美、渡邉裕介、冨松彩佳、佐藤玄基、岩田裕子、荒井勇二、斎藤能彦、中川修
    • Organizer
      第24回日本血管生物医学会学術集会
    • Place of Presentation
      長崎
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] ALK1シグナル伝達系の新規標的遺伝子の探索と発現制御メカニズムの解析2016

    • Author(s)
      久光隆、荒木睦、渡邉裕介、中尾周、藤田匡秀、片山由美、荒井勇二、中川修
    • Organizer
      第24回日本血管生物医学会学術集会
    • Place of Presentation
      長崎
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] Hrt1/Hey1転写調節因子の心血管形態形成における意義2016

    • Author(s)
      深山俊治、藤田匡秀、岩田裕子、渡邉裕介、片山由美、中川修
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 内皮細胞におけるALK1シグナル伝達系の新規下流遺伝子の同定と発現調節機構の解析2016

    • Author(s)
      久光隆、荒木睦、渡邉裕介、中尾周、藤田匡秀、片山由美、中川修
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胎生期血管内皮遺伝子Tmem100の心血管形態形成における発現制御機構と分子機能の解析2016

    • Author(s)
      片山由美、岩田裕子、冨松彩佳、渡邉裕介、斎藤能彦、中川修
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] rt1/Hey1遺伝子の血管内皮発現制御機構におけるNotchおよびALK1シグナリングによる協調的転写調節メカニズム2016

    • Author(s)
      石井修平、渡邉裕介、上本泰生、井原大、久光隆、深山俊治、中川修
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Hrt1/Hey1遺伝子の血管発生における意義と血管内皮発現制御機構における転写調節メカニズム2016

    • Author(s)
      石井修平、渡邉裕介、深山俊治、上本泰生、井原大、久光隆、藤田匡秀、中川修
    • Organizer
      第15回日本心臓血管発生研究会
    • Place of Presentation
      大阪
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Synergistic regulatory mechanisms of endothelial Hrt1/Hey1 gene transcription by Notch and ALK1 signaling pathways.2016

    • Author(s)
      Watanabe Y, Ishii S, Fukayama T, Uemoto T, Ihara D, Hisamitsu T, Arai Y, Nakagawa O:
    • Organizer
      The 9th Notch Meeting
    • Place of Presentation
      静岡
    • Year and Date
      2016-10-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Significance of downstream target nenes of Notch and ALK1 signaling pathways during cardiovascular development and disease.2016

    • Author(s)
      Nakagawa O
    • Organizer
      第2回春期特別日本血管生物医学会シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2016-06-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 血管内皮細胞におけるBMP9/BMP10-ALK1シグナル下流遺伝子群の解析2015

    • Author(s)
      荒木睦、渡邉裕介、坂部正英、久光隆、中尾周、藤田匡秀、片山由美、井岡朋子、中川修
    • Organizer
      日本心血管内分泌代謝学会学術総会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-12-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 血管内皮細胞におけるBMP9/BMP10-ALK1シグナル下流遺伝子群の解析2015

    • Author(s)
      片山由美、渡邉裕介、水田賢、坂部正英、井岡朋子、荒木睦、石井修平、染川智、斎藤能彦、中川修
    • Organizer
      日本血管生物医学会学術総会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-12-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] Na+/H+交換輸送体NHE1とカルシニューリンとの結合に対するGタンパク質共役型受容体刺激の効果2015

    • Author(s)
      久光隆、若林繁夫、中川修
    • Organizer
      日本分子生物学会年会・日本生化学会大会 合同大会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Book] TMEM100, a novel intracellular transmembrane protein essential for cardiovascular development. In Etiology and morphogenesis of congenital heart disease. Ed. by Srivastava D, Keller BB, Markwald R, Yamagishi H, Nakanishi T.2017

    • Author(s)
      Mizuta K, Sakabe M, Somekawa S, Saito Y, Nakagawa O.
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Roles of endothelial Hrt genes for vascular development. In Etiology and morphogenesis of congenital heart disease. Ed. by Srivastava D, Keller BB, Markwald R, Yamagishi H, Nakanishi T.2017

    • Author(s)
      Sakabe M, Morioka T, Kimura H, Nakagawa O.
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Remarks] 国立循環器病研究センター研究所分子生理部

    • URL

      http://www.ncvc.go.jp/res/divisions/molecular_physiology/index.html

    • Related Report
      2017 Annual Research Report 2015 Annual Research Report
  • [Remarks] 国立循環器病研究センター 研究所 分子生理部

    • URL

      http://www.ncvc.go.jp/res/divisions/molecular_physiology/index.html

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2022-10-07  

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