Studies on roles of mechanical forces in the pathogenesis of perinatal diseases
| Project/Area Number |
15K15408
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Osama Woman's and Children's Hospital |
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Principal Investigator |
Matsuo Isao 地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 病因病態部門, 部長 (10264285)
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| Research Collaborator |
Yoshida Chiharu
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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 |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 発生・分化 / 先天性疾患 / メカニカルフォース / 神経管閉鎖不全 / ノンカノニカルWnt / 平面内極性 / 表皮 / 原子間力顕微鏡 / 周産期疾患 / 着床障害 / 先天異常 / 平面内細胞極性 / 哺乳動物胚 / 物理的特性 / ヤング率 / 神経管閉鎖 / メカノセンシング / 幹細胞 |
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| Outline of Final Research Achievements |
Neural tube defects (NTDs), one of the most common congenital disorders are thought to be caused by environmental factors during pregnancy, genetic factors, and the combination of both factors. However, the precise mechanisms underlying the pathogenesis of NTDs remain to be understood. The current project hypothesized that the “loss of robustness or strength in surface ectoderm against mechanical stress during neural tube closure is a primary cause of NTDs pathogenesis”. The mechanical properties of surface ectoderm in wild-type and Grhl3 mutant mouse embryos showing NTDs were measured by atomic force microscopy and the mechanical strength of Grhl3-deficient embryos were shown to be decreased compared to that of wild-type embryos. In addition, Grhl3-induced mechanical strength of surface ectoderm was mediated by the noncanonical Wnt pathway including planar cell polarity genes.
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| Academic Significance and Societal Importance of the Research Achievements |
先天性疾患の発症原因は、遺伝因子や環境因子とその両方の組み合わせによると考えられているが、半数近くは依然として不明である。今回の研究成果は、表皮の物理的強度が低下することで神経管閉鎖不全発症の原因となっている可能性を示唆するものである。更に、本研究成果は、神経管閉鎖障害以外の他の先天性疾患についても、組織や細胞の物理的な強度の異常が、病態発症に関与している可能性を示唆している。今後、本研究結果を基盤に研究を発展させることで、より一般化した仮説の検証を進めていくことが期待される。
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche2019
Author(s)
Kitadate Y., Jorg DJ., Tokue M,. Maruyama A., Ishikawa R., Tsuchiya S., Segi-Nishida E., Nakagawa T., Uchida A., Kimura-Yoshida C., Mizuno S., Sugiyama F., Azami T., Ema M., Noda C., Kobayashi S., Matsuo I., Kanai Y., Nagasawa T., Sugimoto Y., Takahashi S., Simons BD., Yoshida S.
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Journal Title
Cell Stem Cell
Volume: 24
Issue: 1
Pages: 79-92
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Coordinately Co-opted Multiple Transposable Elements Constitute an Enhancer for wnt5a Expression in the Mammalian Secondary Palate.2016
Author(s)
Nishihara H., Kobayashi N., Kimura-Yoshida C., Yan K., Bormuth O., Ding Q., Nakanishi A., Sasaki T., Hirakawa M., Sumiyama K., Furuta Y., Tarabykin V., Matsuo I., and Okada N.
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Journal Title
PLoS Genet.
Volume: 12(10)
Issue: 10
Pages: 1-17
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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