The molecular mechanism by which cells respond to Fluid flow.
| Project/Area Number |
18K14725
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44020:Developmental biology-related
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| Research Institution | National Center of Neurology and Psychiatry (2020)
Institute of Physical and Chemical Research (2018-2019) |
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Principal Investigator |
Minegishi Katsura 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, リサーチフェロー (60568814)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 左右非対称 / 器官形成 / メカノセンサー / RNA結合タンパク質 / Nodal / Cerl2 / Dand5 / Pkd2 / 左右軸 / mRNAの分解 / 機械的刺激 / ノード / 左右非対称性 / node |
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| Outline of Final Research Achievements |
The left-right asymmetric morphogenesis of mammals is triggered by the leftward flow, which is generated by the rotating cilia on the node (E7.5). The mechanism by which flow stimuli is transmitted to the cell, was unknown.
Cerl2 is known as the earliest gene that has left-right asymmetric expression pattern. Cerl2 is expressed higher on the right side of node. This left-right asymmetric expression of Cerl2 is generated by the left side specific degradation of mRNA of Cerl2. The degradation of Cerl2 is induced by fluid flow stimuli via cation channel Pkd2. In this research, I found that the most proximal 200 nucleotide region of the 3'-UTR is essential for the asymmetric mRNA decay. I also demonstrated that RNA binding protein Bicc1 bind to the region, and CCR4-NOT is involved in the degradation mechanism of Cerl2. I expected that this study will lead the elucidation of the mechanism by which mechanical stimuli regulates gene expression.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞に加わる機械的刺激による遺伝子発現の制御は発生、加齢、メタボリズム、循環器の維持など多岐にわたる生命現象に関与している。本研究は機械刺激が遺伝子発現の左右差をもたらすメカニズムについての研究であるが、左右非対称な形態形成の理解にとどまらず、広く生物学に影響を与える一般的な原理、機構へと発展する可能性を秘めている。例えば、今回解析したPkd２は腎臓上皮細胞の繊毛に局在し水流のセンサーとしてはたらくことが報告されており、その機能欠損が嚢胞腎を引き起こすことも知られている。このことから、我々はノードと腎臓細胞において類似した機械的刺激を変換する機構が存在しているのではないかと考えている。
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Report
(4 results)
Research Products
(7 results)
