Elucidation of the mechanism of cleft palate pathogenesis caused by abnormal epigenetic regulation

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K10398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Higashihori Norihisa 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (50585221)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 口蓋裂 / 先天異常 / エピジェネティック / ヒストンメチル化酵素 / 神経堤細胞

Outline of Final Research Achievements

Recently, it has been reported that epigenetic regulations are involved in the pathogenesis of congenital abnormalities, including cleft palate. The purpose of this study was to investigate how an abnormality in an enzyme involved in histone methylation (SETDB1), one of the epigenetic regulation mechanisms, affects the development of the palate.
When mice were analyzed in which Setdb1 was specifically deleted in cells derived from neural crest cells that differentiate into bone and cartilage in the maxillofacial region, all fetuses showed cleft palate. The reduced proliferative capacity of the cells and decreased expression of genes thought to be important in palatal development were suggested to be factors in the development of cleft palate, indicating that epigenetic regulations are important in palatal development.

Free Research Field

歯科矯正学

Academic Significance and Societal Importance of the Research Achievements

口唇裂・口蓋裂は、高頻度（1/600人）にみられ、その治療には、矯正歯科医を始め、小児歯科医、口腔外科医、形成外科医、言語療法士など、様々な専門家による長期に渡る治療が必要であり、患者、またその両親の身体・精神・経済的負担は大きい。従って、分子生物学見地から口唇裂・口蓋裂の発生機序をより良く解明する事は、発症率および症状の軽減をはかり、患者の負担の軽減につながる。また、従来よりがんと先天異常は共通したシグナルを介することが多いとの報告からも、本研究から得られる知見は顎顔面領域の発生だけでなく、がん研究など他分野の研究にも応用が可能と考えられ、医学全体に多大な進歩をもたらすものと考える。