| Project/Area Number |
17KT0114
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 特設分野 |
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| Research Field |
Constructive Systems Biology
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| Research Institution | Institute of Physical and Chemical Research (2018-2019)
Okinawa Institute of Science and Technology Graduate University (2017) |
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Principal Investigator |
Yasuoka Yuuri 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (70724954)
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| Project Period (FY) |
2017-07-18 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 進化発生 / 収斂伸長運動 / 液胞 / 細胞外基質 / ケラタン硫酸 / ナメクジウオ / ツメガエル / ゲノム編集 / 発生 / 細胞膜輸送 / 進化 / 数理モデル |
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| Outline of Final Research Achievements |
Notochord is defined as a vacuolated supporting organ of larval tail, which characterizes chordates. Here I proposed a self-organizing morphogenetic mechanism forming the notochord rod controlled by vacuolation, membrane trafficking, extracellular matrix formation, and cell proliferation; named "turgor pressure-sheath strength model." As a part of this model, I examined keratan sulfate biosynthesis in Xenopus embryos. Among carbohydrate sulfotransferase genes, chst3 and chst6 were identified as notochord-enriched genes. Loss of function analysis demonstrated that they were required for keratan sulfate synthesis in the notochord.
To examine evolutionary conservation of notochord components, I investigated expression patterns of notochord related genes in amphioxus embryos by in situ hybridization. The result suggests that caveolin, calumenin, leprecan, and so on have functioned as ancestral notochord components since chordate arose.
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| Academic Significance and Societal Importance of the Research Achievements |
【学術的意義】脊索は脊椎動物を含む脊索動物を特徴づける器官だが、その細胞生物学的な性質を俯瞰的にとらえた研究は少ない。本研究で提唱した「液胞膨圧ー脊索鞘強度平衡モデル」は、これまでの知見を合理的にまとめた優れたモデルであり、今後その詳細な分子メカニズムの解明が期待される。また、ナメクジウオの遺伝子発現パターンを明らかにし、祖先的な脊索構成要素の一部を明らかにできたのも大変意義深い。
【社会的意義】脊索遺残組織は椎間板髄鞘としてヒト成体にも存在し、その損傷は腰痛などの原因となる。また、椎間板髄鞘から生じる腫瘍（脊索腫）が希少疾患として知られている。本研究はこれらの疾患研究の基礎となりうる。
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