Analysis of mechanism of palatal fusion for new therapy of cleft palate

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K15737
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Osaka University
• Principal Investigator: Sakai Takayoshi 大阪大学, 歯学研究科, 教授 (90379082)
• Co-Investigator(Kenkyū-buntansha): 野原 幹司 大阪大学, 歯学研究科, 准教授 (20346167)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 口蓋裂

Outline of Final Research Achievements

Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip microarrays. Periostin and Tenascin C were highly up-regulated before and after palate formation. We have focused on characterized expression of extracellular matrix during soft palate development, including Periostin and Tenascin C. The immunohistochemical expression of Postn and TnC appeared to be wider and more clearly defined in posterior palatal mesenchyme before/after palatal fusion. These results indicate that TnC is an important extracellular matrix protein in soft palate development and is paracrine regulated by TGF-β in the palatal epithelium.

Free Research Field

外科系歯学

Academic Significance and Societal Importance of the Research Achievements

唇顎口蓋裂とは、口唇、歯槽部、口蓋などの口腔顎顔面領域に披裂を生じる先天異常であり、遺伝的要因と環境的要因の両者が複雑に関係していると言われている。胎生期に口蓋が癒合する仕組みを明らかにし、新しい治療法を確立するために本計画を推進した。まず胎生期口蓋上皮に発現する遺伝子を網羅的に含む遺伝子のデータベースを作成し、その中から口蓋癒合前後に発現する遺伝子を探索した。PeriostinとTenascin Cは、癒合前後の口蓋後方の間葉組織に広く発現しており、口蓋形成に重要なTGF-βシグナルによって制御されていることが明らかになった。