Molecular basis of glossopharyngeal nerve formation during pahryngeal arch development

2019 Fiscal Year Final Research Report

• Project/Area Number: 26460257
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Kitasato University
• Principal Investigator: Okubo Tadashi 北里大学, 医学部, 准教授 (10450719)
• Project Period (FY): 2014-04-01 – 2020-03-31
• Keywords: 舌咽神経 / Ripply3 / 咽頭弓 / 味蕾形成 / レチノイン酸シグナル / プロモーター制御

Outline of Final Research Achievements

Pharyngeal arch (PA) is a transient segmental structure, and it is important for the later peripheral neurogenesis. Ripply3 is highly expressed in the developing PA of mouse. To explore the regulatory mechanism underlying between PA formation and glossopharyngeal nerve (GN) development, we focused on the involvement of Ripply3. Consequently, we found Ripply3 is required for GN development. Next, we identified retinoic acid (RA) is required for the enhancement of Ripply3 expression. Ripply3 promoter analysis revealed that RA and Ripply3 cooperatively participate in PA and GN development. We also found that Ripply3 expressing cells give rise to GN ganglia by using cre reporter system. Some candidates of Ripply3 interacting genes were identified. Among them, Paxilin is involved in morphogenesis of PA with Ripply3, and Glyr1 is a novel factor regulates the transcriptional property of Ripply3. Thus, we gained new insights into the Ripply3 function in GN formation during PA development.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

脊椎動物の胎児期に現れる咽頭弓は、その後様々器官形成に関与する。ヒトのDiGeorge症候群ではTBX1の欠失により咽頭弓の形成不全に続く心臓、胸腺そして末梢神経の形成異常が起こる。我々は、これまでにマウスTbx1の転写抑制因子としてRipply3を同定し、咽頭弓分節に必須な遺伝子であることを報告したが、Ripply3が舌咽神経の形成に関与しているか不明であった。本研究は、Ripply3と咽頭弓分節、舌咽神経節形成との連関を明らかにし、その背後にある分子機構の一端を解明するに至った。また近年ヒトRIPPLY3にも変異が見つかっており、ヒト先天性異常の発症機構を理解する上で重要な研究といえる。