The formation of nerve bundles, which is partially regulated by neural cell adhesion molecule 1 (NCAM1), is important for neural network organization during peripheral nerve regeneration. However, little is known about how the extracellular matrix (ECM) microenvironment affects this process. Here, we seeded dorsal root ganglion tissue blocks on different ECM substrates of peripheral nerve ECM-derived matrix-gel, Matrigel, laminin 521, collagen I, and collagen IV, and observed well-aligned axon bundles growing in the peripheral nerve ECM-derived environment. We confirmed that NCAM1 is necessary but not sufficient to trigger this phenomenon. A protein interaction assay identified collagen VI as an extracellular partner of NCAM1 in the regulation of axonal fasciculation. Collagen VI interacted with NCAM1 by directly binding to the FNⅢ domain, thereby increasing the stability of NCAM1 at the axolemma. Our in vivo experiments on a rat sciatic nerve defect model also demonstrated orderly nerve bundle regeneration with improved projection accuracy and functional recovery after treatment with 10 mg/mL Matrigel and 20 μg/mL collagen VI. These findings suggest that the collagen VI-NCAM1 pathway plays a regulatory role in nerve bundle formation. This study was approved by the Animal Ethics Committee of Guangzhou Medical University (approval No. GY2019048) on April 30, 2019.

Jia-Hui Sun

Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University,Key Laboratory of Neurogenetics and Channelopathiesof Guangdong Province and the Ministry of Education of China,Guangzhou,Guangdong Province,China;Key Laboratory of Neurological Function andHealth,School of Basic Medical Sciences,Guangzhou Medical University,Guangzhou,Guangdong Province,China;Zhongshan School of Medicine,Sun Yat-sen University,Ministry of Education,Guangzhou,Guangdong Province,China;Department of Pharmacy,Hospital of Stomatology,Guanghua School ofStomatology,Sun Yat-sen University,Guangzhou,Guangdong Province,China;Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education,School of Chemistry,Sun Yat-sen University,Ministry of Education,Guangzhou,Guangdong Province,China;Department of Orthopedic Trauma and Microsurgery,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong Province,China

中国神经再生研究（英文版）

[1]Jia-Hui Sun-.Nerve bundle formation during the promotion of peripheral nerve regeneration: collagen VI-neural cell adhesion molecule 1 interaction)[J].中国神经再生研究（英文版）,2022(05):1023-1033

fasciculation,axolemma,GY2019048

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