Molecular mechanisms governing tongue morphogenesis in embryonic mice

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09822
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: The Nippon Dental University
• Principal Investigator: Taya Yuji 日本歯科大学, 生命歯学部, 教授 (30197587)
• Co-Investigator(Kenkyū-buntansha): 豊田 健介 日本歯科大学, 生命歯学部, 准教授 (40585874) ; 添野 雄一 日本歯科大学, 生命歯学部, 教授 (70350139) ; 佐藤 かおり 日本歯科大学, 生命歯学部, 講師 (90287772)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 舌形態形成 / 上皮間葉相互作用 / 分子ネットワーク

Outline of Final Research Achievements

In this study, we focused on the signaling molecules that act in tongue morphogenesis and investigated their molecular regulatory mechanisms. In the search for signaling molecules, expression of Shh, Patched1, Igf1, and Bmp4 was upregulated during the formation of the lateral lingual swellings (LLS). Endothelin-1 (ET-1) signaling was found to be an upstream molecule of Shh, Bmp4, and Fgf8 expressed in the epithelium of LLS. The microtia in ET-1-deficient mice and in Shh knockdown in an organ culture was thought to be due to the inability of muscle progenitor cells to make contact with the epithelium of the medial mandibular arches (MA), resulting in a non-muscle lineage mesenchymal cell population that lost proliferative activity and suppressed the formation of the LLS. Taken together, these findings reveal molecular regulatory mechanisms that operate in the cell-to-cell interactions among the coating epithelium, tongue muscle and non-muscle mesenchyme in the morphogenesis of tongue.

Free Research Field

顎顔面発生

Academic Significance and Societal Importance of the Research Achievements

舌は咀嚼や嚥下・構音などの口腔機能において重要な器官であり、舌癌での切除手術後の舌再建や無舌症・小舌症などの先天異常ではその機能障害が問題となっている。舌の再生医療や疾患治療の実現には、舌発生の時期からの知見を集積していくことが重要と考える。