Molecular signaling pathways regulating the formation of nociceptive neuronal network

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04660
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kamiguchi Hiroyuki 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (10233933)
• Research Collaborator: Inoue Mariko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 軸索 / ガイダンス / 表皮 / 神経成長因子 / イノシトール３リン酸 / ホスファチジン酸

Outline of Final Research Achievements

During developmental targeting of nociceptive axons toward the skin epidermis, the axon continues to be exposed to increasing concentrations of nerve growth factor (NGF), an attractive cue released from the epidermis. Therefore, the axon should be able to regulate its sensitivity to wide rages of NGF concentrations. This project has identified the IP3 receptor type 3, an intracellular protein that responds to the axon-attractive molecule IP3, as a critical regulator of axonal sensitivity to NGF and of axonal targeting to the skin epidermis. Furthermore, this project has identified phosphatidic acid, an intracellular lipid molecule that mediates attractive axon guidance in the skin through regulating cellular membrane dynamics in the axon.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

痛覚を担う神経細胞の突起（軸索）が皮膚の表面（表皮）へ投射する仕組みを、表皮由来の誘引性分子への感受性制御および軸索細胞内の膜ダイナミクス制御の両面から明らかにした。これらの成果は、神経軸索が細胞外環境の誘引性分子を認識して正しい標的へ到達する仕組みの理解に貢献するとともに、皮膚への神経投射が関与しうる病態（例えば、痒み）のメカニズム解明および治療法開発に寄与しうる成果である。