| Project/Area Number |
24591618
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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 |
Embryonic/Neonatal medicine
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| Research Institution | Research Institute, Osaka Medical Center for Maternal and Child Health |
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Principal Investigator |
SHIBUKAWA Yukinao 地方独立行政法人大阪府立病院機構大阪府立母子保健総合医療センター(研究所), その他部局等, 研究員 (90393264)
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| Co-Investigator(Kenkyū-buntansha) |
DAIMON Etsuko 母子センター研究所, 代謝部門, 研究技術員 (90581314)
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| Research Collaborator |
YAMAZAKI Natsuko 母子センター研究所, 代謝部門, 研究補助員
IAWAI Kaori 母子センター研究所, 代謝部門
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 体腔閉鎖 / 神経管閉鎖 / 眼瞼閉鎖 / 細胞骨格 / 細胞移動 / 収縮 / 細胞融合 / 体壁閉鎖 / NTD / アクチン細胞骨格 |
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| Outline of Final Research Achievements |
To explore the physiological role of CNN3, we generated CNN3 null mice and reveals that 34% of homozygous exhibits neural tube and eyelid closure defects. During neural tube closure (NTC), CNN3 is apically localized in neuroepithelial (NE) cells and well co-localized with F-actin. CNN3-mutant NE cell show a reduction in apically not only F-actin accumulation but MLC phosphorylation. We identified that MHCIIA is a key binding partner of CNN3 and Ser293/296 phosphorylation of CNN3 is critical for this association. Moreover, ROCK1/2 and Shroom3 localization is also disrupted in homozygous embryo. During eyelid development, CNN3 mutant mice shows impaired or delayed extension of the eyelid epithelial sheet with disorganized actin bundles at the peridermal cells in the leading edge of the sheet. These results demonstrate that CNN3 is required for stabilization of actomyosin cable and apically localized ROCKs during normal progression of body wall closure.
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