the roles of heparan sulfate on neural crest cells function during craniofacial and tooth development

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10380
• 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: Osaka University
• Principal Investigator: Ayaka Oka 大阪大学, 歯学研究科, 助教 (20635403)
• Co-Investigator(Kenkyū-buntansha): 犬伏 俊博 大阪大学, 歯学研究科, 講師 (30550941) ; 黒坂 寛 大阪大学, 歯学部附属病院, 講師 (20509369) ; 山城 隆 大阪大学, 歯学研究科, 教授 (70294428)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: へパラン硫酸 / 糖鎖 / 口蓋裂 / 不正咬合

Outline of Final Research Achievements

In the present study, we aimed to clarify the roles of heparan sulfate (HS) on neural crest cells function during craniofacial and tooth development by the conditional knockout mice model. We generated conditional knockout mice by deleting the Ext1 (Ext1-CKO mice) which is involved in HS biosynthesis, and examined the craniofacial developmental phenotype in the Ext1-CKO mice. The Ext1-CKO mice showed severer craniofacial abnormalities with midline cranial bone defects including cleft palate, short mandible, and small maxilla, as well as reduced size and malformation of tooth germ. In addition, our results indicated that HS plays an essential role in the craniofacial and tooth morphogenesis by regulating neural crest cells migration. We also demonstrated that Wnt/β-catenin signaling is significantly impaired in Ext1-CKO mice, by comprehensive RNA-sequencing approach and reporter mice model. The results might contribute to improve clinical diagnosis for craniofacial anomalies.

Free Research Field

発生

Academic Significance and Societal Importance of the Research Achievements

本研究は、へパラン硫酸による頭蓋顎顔面や歯の形態形成制御機構の詳細を明らかにしようというはじめての試みであり、本研究成果はGAG糖鎖合成/代謝異常を原因とする先天異常症候群のメカニズムの解明や従来では治療が困難であったそれらの先天異常症候群に対する新しい治療法開発につながると考えられる。さらに、歯をはじめとした新規組織再生法開発に繋がることが強く期待される。