SEMA3B switches axon-axon to axon-glia interactions required for unmyelinated axon envelopment and integrity
Li Liu,
Zhigang Gao,
Xueyuan Niu,
Hong Yu,
Xiaolong Xin,
Yanlan Gu,
Genghai Ma,
Yan Gu,
Yijun Liu,
Sanhua Fang,
Till Marquardt () and
Liang Wang ()
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Li Liu: Zhejiang University School of Medicine
Zhigang Gao: National Clinical Research Center for Child Health
Xueyuan Niu: Wenzhou Medical University
Hong Yu: Zhejiang University School of Medicine
Xiaolong Xin: Zhejiang University School of Medicine
Yanlan Gu: Zhejiang University School of Medicine
Genghai Ma: Qixia City People’s Hospital
Yan Gu: Zhejiang University School of Medicine
Yijun Liu: Zhejiang University School of Medicine
Sanhua Fang: Zhejiang University School of Medicine
Till Marquardt: RWTH Aachen University
Liang Wang: Zhejiang University School of Medicine
Nature Communications, 2025, vol. 16, issue 1, 1-19
Abstract:
Abstract During peripheral nerve (PN) development, unmyelinated axons (nmAs) tightly fasciculate before being separated and enveloped by non-myelinating Schwann cells (nmSCs), glial cells essential for maintaining nmA integrity. How such a switch from axon-axon to axon-glia interactions is achieved remains poorly understood. Here, we find that inactivating SC-derived SEMA3B or its axonal receptor components in mice leads to incomplete nmA separation and envelopment by nmSCs, eliciting hyperalgesia and allodynia. Conversely, increasing SEMA3B levels in SCs accelerates nmA separation and envelopment. SEMA3B transiently promotes nmA defasciculation accompanied by cell adhesion molecule (CAM) endocytosis, subsequently facilitating nmA-nmSC association. Restoring SEMA3B expression following PN injury promotes nmA-nmSC re-association and alleviates hyperalgesia and allodynia. We propose that SEMA3B-induced CAM turnover facilitates a switch from axon-axon to axon-glia interactions promoting nmA envelopment by nmSCs, which may be exploitable for alleviating PN injury-induced pain by accelerating the restoration of nmA integrity.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61318-8
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DOI: 10.1038/s41467-025-61318-8
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