Elucidation of tissue-specific morphogenetic mechanism regulated by glycolytic activity
| Project/Area Number |
15K07084
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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 | 一般 |
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| Research Field |
Developmental biology
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| Research Institution | Doshisha University |
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Principal Investigator |
Sakai Daisuke 同志社大学, 研究開発推進機構, 助教 (90632646)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 解糖系 / 神経管閉鎖 / 低酸素 |
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| Outline of Final Research Achievements |
To investigate the correlation between hypoxia and embryonic development, we focused on the anaerobic glycolysis, the cellular metabolism under hypoxia. Whole-embryo culture of mid-gestation embryos with glycolytic inhibitors caused neural tube closure defects at cranial levels without cell death. Therefore, anaerobic glycolytic activity seems to be essential for neural plate bending associated with cell shape changes. Consistent with this, we observed suppression of apical constriction and reduction of phosphorylated myosin light chain 2, activator of actin contraction in neuroepithelial cells of inhibitor-treated embryos. Our gene expression analyses demonstrated that some hypoxia-responsive glycolytic enzyme genes were specifically expressed in neural plate of mid-gestation embryos. Taken together, intrauterine hypoxic condition regulates neural plate bending via tissue-specific activation of glycolysis.
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| Academic Significance and Societal Importance of the Research Achievements |
胚の形態形成というイベントは遺伝的プログラムによって進行すると考えられてきた。本研究では、胚を取り巻く環境が遺伝的プログラムを修飾し、形態形成を制御する可能性を検討した。本研究の成果により、子宮内の低酸素環境が細胞内の代謝系の活性化を介して、神経管閉鎖という胚発生過程で最もダイナミックな形態形成過程の一つを制御することが明らかとなった。これにより、新規の環境因子依存的な発生メカニズムの存在が明るみとなった。神経管閉鎖不全は無脳症や二分脊椎症などの先天性障害の原因であり、妊娠期の葉酸欠乏が原因であると考えられている。本研究成果により、解糖系代謝異常もこれらの原因となり得ることが示された。
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Report
(5 results)
Research Products
(12 results)
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[Journal Article] Mllt10 knockout mouse model reveals critical role of Af10-dependent H3K79 methylation in midfacial development2017
Author(s)
2.Honami Ogoh, Kazutsune Yamagata, Tomomi Nakao, Lisa L. Sandell, Ayaka Yamamoto, Aiko Yamashita, Naomi Tanga, Mai Suzuki, Takaya Abe, Issay Kitabayashi, Toshio Watanabe, Daisuke Sakai
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Journal Title
Scientfic Reports
Volume: 7
Issue: 1
Pages: 11922-11922
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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