| Project/Area Number |
17K15551
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 神経管閉鎖 / 二分脊椎 / 解剖学 / ユビキチン化 / 発生学 / 発生・分化 |
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| Outline of Final Research Achievements |
We previousely revealed that the planar cell polarity (PCP) protein Vangl2 is essential to form normal dendritic spine by interacting with cell adhesion molecule N-cadherin physically. However, it is unknown whether N-cadherin is included in the PCP signaling pathway. In this study, we investigated whether this interaction also affects neural tube closure and inner ear development are regulated by PCP pathway. In mouse embryos, both N-cadherin and Vangl2 were expressed in the neural plate and neural tube and partially colocalized. We are also analyzing the occurrence of the inner ear. In the course of this study, we revealed that ubiquitination of Vangl2 promotes the degradation of Prickle2 in mammalian cells.
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| Academic Significance and Societal Importance of the Research Achievements |
二分脊椎症は神経管閉鎖異常が原因の難病で、妊娠前から妊娠中の女性の葉酸摂取により予防が可能であるが、約20%の症例では遺伝子異常が原因のため予防は困難である。この異常にはVangl2を含むPCP因子も含まれる。本研究ではVangl2とNカドヘリンの遺伝学的相互作用が神経管閉鎖に重要であることを示した。PCP複合体とカドへリン複合体との間の相互作用が細胞接着の形成を調節することがより普遍的なものである可能性を示唆しているが、更に研究が必要である。本研究を更に発展させることで、Vangl2/N-カドヘリンが神経管形成に果たす役割を明らかにでき、二分脊椎の発生原因の解明に繋がることが期待される。
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