Elucidation for regulation of axonal extension and sensory recovery by Hedgehog signaling

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K19225
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Niigata University
• Principal Investigator: Sato-Yamada Yurie (山田友里恵) 新潟大学, 医歯学系, 助教 (20804537)
• Project Period (FY): 2021-11-01 – 2024-03-31
• Keywords: 末梢神経 / 神経再生 / Hedgehogシグナル / 血管周囲細胞 / Gli1

Outline of Final Research Achievements

We observed that Hh signaling responsive cells [Gli1(+) cells] in both the perineurium and endoneurium. In the endoneurium, Gli1(+) cells were classified as blood vessel associated or non-associated. After injury, Gli1(+) cells around blood vessels mainly proliferated to then accumulate into the injury site along with endothelial cells. Hh signaling activity was retained in Gli1(+) cells during nerve regeneration. To understand the role of Hedgehog signaling in Gli1(+) cells during nerve regeneration, we examined mice with Gli1(+) cells-specific inactivation of Hh signaling (Smo cKO). After injury, Smo cKO mice showed significantly reduced numbers of accumulated Gli1(+) cells along with disorganized vascularization at an early stage of nerve regeneration, which subsequently led to an abnormal extension of the axon. Thus, Hh signaling in Gli1(+) cells appears to be involved in nerve regeneration through controlling new blood vessel formation at an early stage.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

末梢神経再生の分子メカニズムの詳細は分かっていない。そのため、神経損傷の根本的治療薬は現存しない。本研究では、損傷神経で活性化する、Hedgehogシグナルに着目して神経再生の分子機構の一部を明らかにした。Cre-loxPシステムを用いて神経再生過程におけるHhシグナルの発現時期と部位を、自由にコントロールし、Hhシグナルのバランスの揺らぎを人為的に再現する実験系を用いた。これによりHhシグナルの神経再生における詳細なメカニズムを検討することができた。本研究で得られた知見は神経の再生機構に基づく新たな末梢神経再生治療法の確立に寄与する可能性がある。