| Project/Area Number |
18K09841
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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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| Review Section |
Basic Section 57070:Developmental dentistry-related
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
和中 明生 奈良県立医科大学, 医学部, 教授 (90210989)
下村 忠弘 奈良県立医科大学, 医学部附属病院, 研究員 (90645607)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 発生・分化 / 細胞・遺伝子 / シグナル伝達 / 歯学 / 成長・発育 / 細胞・組織 / 上顎 / 遺伝子 / 歯科矯正学 / 細胞分化・組織形成 |
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| Outline of Final Research Achievements |
Cleft lip with or without cleft palate (CLP) usually results from a failure of the medial nasal
prominences to fuse with the lateral and maxillary prominences. This failure inhibits facial morphogenesis regulated by several major morphogenetic signaling pathways. We hypothesized that CLP results from the failure of the Wnt signaling pathway. We applied beads soaked with Dickkopf-1 (Dkk-1), Alsterpaullone (AL) or Wnt3a to the right side of the maxillary prominence of the chick embryo. The embryo showed a defect of the maxilla on the treated side, and skeletal staining revealed hypoplasia of the premaxilla and palatine bone as a result of Dkk-1-soaked bead implantation. Maxillary prominence treated with Dkk-1, which indicated that the deformity of the maxillary bone was controlled by gene targets of the Wnt signaling pathway. Wnt signaling might regulate N-cadherin expression via Msx1, resuliting in cell aggregation for osteochondrogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
われわれは、これまで顎顔面の形成過程を司る分子シグナル機構を調べてきた。顔面の形成は胎生期、顔面突起が前下方に成長し、上顎突起と前頭鼻突起が癒合し（EMT)上口唇が形成される。唇顎裂発症においてはEMTが作用していないのではとの仮説を立て、今年度はEMTに作用する遺伝子シグナル作用について調べた。Dkk-1を用いてWNTシグナルを阻害するとEMTに作用する遺伝子の発現が減少し、唇顎裂を生じることが明らかとなった。したがって、すなわち口唇裂発症の原因はWNTシグナルをはじめとする顎顔面の形成過程を司る分子シグナル伝達がうまく行われていなかったことが考えられる。
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