Deciphering of left-right asymmetry -Identification of new molecules during L-R determination and proof of
Project/Area Number |
16H02618
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General physiology
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Research Institution | National Cardiovascular Center Research Institute |
Principal Investigator |
MOCHIZUKI NAOKI 国立研究開発法人国立循環器病研究センター, 研究所, 研究所長 (30311426)
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Research Collaborator |
Fukui Hajime 国立循環器病研究センター, 研究所細胞生物学部所属
Ando Koji 国立循環器病研究センター, 研究所細胞生物学部所属
Miyazaki Takahiro 国立循環器病研究センター, 研究所細胞生物学部所属
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥44,590,000 (Direct Cost: ¥34,300,000、Indirect Cost: ¥10,290,000)
Fiscal Year 2018: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2017: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2016: ¥22,490,000 (Direct Cost: ¥17,300,000、Indirect Cost: ¥5,190,000)
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Keywords | 左右差 / クッパ―胞 / Hippo シグナル / ゼブラフィッシュ / 繊毛 / 発生 / Hippo / カルシウム / 非対称 / Yap1 / Wwtr1 / 左右非対称 / 心臓前駆細胞 / 心臓形成 / Hippoシグナル / Kupffer's vesicle / sox17 / Arl13b |
Outline of Final Research Achievements |
Left-right asymmetry is essential for body planning as well as anterior-posterior and dorsal-ventral axes. We focused on the mechanism by which kupffer's vescile (KV) and cilia in the KV are organized during zebrafish embryogenesis. In the classical pathway, left-right flow in the KV promoted by the rotation of cilia results in the asymmetric distribution of factors that determines the localization of progenitor cells of organs. We developed transgenic zebrafish lines that enabled us to monitor KV cells and cilia and that enables us to visualize Ca oscillation in the KV cells. By monitoring the KV formation and cilia development, we demonstrated that Ca oscillation starts before the lumen forms inside of the KV, suggesting that Ca oscillation does not depend on the flow caused by the rotation of cilia. Furthermore, we found that Hippo signaling is dispensable for KV formation followed by cilia fomation but indispensable for correct organ distribution.
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Academic Significance and Societal Importance of the Research Achievements |
生命現象の根幹である体の前後、背腹、左右を決定する機構の解明は発生学、生物学の問題として重要である。この中で本研究では、左右差形成機構の解明を目的とした。クッパ―胞という発生時に一過性に生じる器官内に流れが生じて左右決定因子の不均等分布が生じることが、左右差決定の古典的なメカニズムと考えられてきた。しかし、本研究でクッパ―胞の内腔が形成される以前からカルシウムの濃度の不均一性がクッパ―胞形成細胞群に見られることがわかり、新たな左右差形成機構の存在が示唆された。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] A molecular atlas of cell types and zonation in the brain vasculature2018
Author(s)
Vanlandewijck M, He L,MA, Andrae J, Ando K, Del Gaudio F, Nahar K, Lebouvier T, Lavi B, Gouveia L, Sun Y, Raschperger EM, Zarb Y, Mochizuki N, Keller A, Lendahl U, Betsholtz C.
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Journal Title
Nature
Volume: 554
Issue: 1
Pages: 475-480
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] A molecular atlas of cell types and zonation in the brain vasculature.2018
Author(s)
Vanlandewijck M, He L, Mae MA, Andrae J, Ando K, Del Gaudio F, Nahar K, Lebouvier T, Lavin;a B, Gouveia L, Sun Y, Raschperger E, Rasanen M, Zarb Y, Mochizuki N, Keller A, Lendahl U, Betsholtz C.
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Journal Title
Nature
Volume: 554
Issue: 7693
Pages: 475-480
DOI
Related Report
Peer Reviewed
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[Journal Article] Guidelines for morpholino use in zebrafish.2017
Author(s)
Stainier DYR, Raz E, Lawson ND, Ekker SC, Burdine RD, Eisen JS, Ingham PW, Schulte-Merker S, Yelon D, Weinstein BM, Mullins MC, Wilson SW, Ramakrishnan L, Amacher SL, Neuhauss SCF, Meng A, Mochizuki N, Panula P, Moens CB.
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Journal Title
PLoS Genet.
Volume: 13
Issue: 10
Pages: e1007000-e1007000
DOI
Related Report
Peer Reviewed
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[Journal Article] Flow-dependent endothelial YAP regulation that contributes to vessel maintenance.2017
Author(s)
Nakajima H, Yamamoto K, Agarwala S, Terai K, Fukui H, Fukuhara S, Ando K, Miyazali T, Yokota Y, Sxhmelzer E, Belting H, Affolter M, Lecaudey, Mochizuki N
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Journal Title
Developmental Cell
Volume: 40
Issue: 6
Pages: 523-536
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Osteocrin, a secretory peptide from heart, contributes to cranial osteogenesis in zebrafish2016
Author(s)
Chiba A, Watanabe-Takano H, Terai K, Fukui H, Miyazaki T, Uemura M, Hashimoto H, Hibi M, Fukuhara S, Mochizuki N
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Journal Title
Development
Volume: 144
Pages: 334-344
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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