| Project/Area Number |
17390552
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthodontic/Pediatric dentistry
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| Research Institution | Okayama University (2006)
Osaka University (2005) |
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Principal Investigator |
YAMASHIRO Takashi Okayama University, Graduate Shool of Medicine, Dentistry and Pharmaceutical Science, Professor (70294428)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Teruko Tohoku University, Graduate School of Dentistry, Professor (00127250)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥15,600,000)
Fiscal Year 2006: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2005: ¥10,500,000 (Direct Cost: ¥10,500,000)
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| Keywords | cleft palate / Runxl / Epithelial-msenchymal interaction / Fgf18 / primary palate / secondary palate / epithelial fusion / ノックアウトマウス / 口蓋上皮 / コンディショナルレスキュー |
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| Research Abstract |
Runxl is expressed in the medial edge epithelial cells of the palatal shelf. We herein describe the functional roles of Runxl in palatogenesis and the regulatory mechanisms of Runxl expression. Runxl-deficient mice die prior to palatogenesis due to impaired hematopoiesis, and this embryonic lethality was rescued by introducing Runxl expression under the control of the GATA-1 promoter in the Runx1 mutants. Runxl deficiency results in anterior clefting between the primary and the secondary palate, and at the first rugae regions between the primary palates. The nasal septum does not fuse to the secondary palate. In the control mice, an SEM analysis revealed that the fusing epithelial surface exhibited a rounded cobblestone-like appearance. In contrast, such cellular prominence was less evident in the Runxl mutants. These findings indicated that Runxl is involved, as a novel function, in the epithelial fusion in the anterior part of the palate. We also evaluated the possible overlapped expression among Runx genes in the fusing epithelium along the anterior-posterior axis. The middle parts of the palatal process showed an overlapped expression of Runxl and Runx2. In contrast, the anterior palate showed only Runxl expression. It is possible that the anterior clefting in Runxl mutants might be explained by a functional redundancy. In addition, we also report that Fgf-18 is expressed in the mesenchyme underlying the fusing epithelium during palatal fusion. Therefore, we explored the possible induction of Runxl by Fgfl8 proteins in bead experiments. Fgf18 beads induced ectopic Runxl expression in the epithelium of the palatal explants. These finding indicated that epithelial Runxl is induced by mesenchymal Fgf18 signaling. These data showed a novel function of Runxl in palatogenesis, and this function is regulated by an epithelial-mesenchymal interaction between the mesenchymal Fgf signaling and the epithelial Runxl expression.
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