The role of retinoid signaling in pathogenesis of choanal atresia and stenosis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H05687
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Osaka University
• Principal Investigator: Kurosaka Hiroshi 大阪大学, 歯学部附属病院, 講師 (20509369)
• Co-Investigator(Renkei-kenkyūsha): Yamashiro Takashi 大阪大学, 大学院・歯学研究科, 教授 (70294428)
• Research Collaborator: Nakaya Akihiro
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 顎顔面形成不全 / 後鼻孔閉鎖 / 口唇口蓋裂 / レチノイン酸シグナル

Outline of Final Research Achievements

Craniofacial development is a complex process that involves sequential growth and fusion of the facial prominences. When these processes fail, congenital craniofacial anomalies can occur. For example, choanal atresia (CA) is a congenital craniofacial anomaly in which the connection between the nasal airway and nasopharynx is completely blocked. In this study, we discovered that mice with mutations in retinol dehydrogenase 10 (Rdh10), which perturbs Vitamin A metabolism and retinoid signaling, exhibit fully penetrant CA. Interestingly, we demonstrate Rdh10 is specifically required in non-neural crest cells prior to E10.5 for proper choanae formation, and that in the absence of Rdh10, Fgf8 is ectopically expressed in the nasal fin. Taken together, our findings demonstrate that RDH10 is essential during the early stages of facial morphogenesis for the formation of a functional nasal airway, and furthermore establish Rdh10 mutant mice as an important model system to study CA.

Free Research Field

顎顔面発生