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N-Cadherin is Involved in Neuronal Activity-Dependent Regulation of Myelinating Capacity of Zebrafish Individual Oligodendrocytes In Vivo

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Abstract

Stimulating neuronal activity increases myelin sheath formation by individual oligodendrocytes, but how myelination is regulated by neuronal activity in vivo is still not fully understood. While in vitro studies have revealed the important role of N-cadherin in myelination, our understanding in vivo remains quite limited. To obtain the role of N-cadherin during activity-dependent regulation of myelinating capacity of individual oligodendrocytes, we successfully built an in vivo dynamic imaging model of the Mauthner cell at the subcellular structure level in the zebrafish central nervous system. Enhanced green fluorescent protein (EGFP)-tagged N-cadherin was used to visualize the stable accumulations and mobile transports of N-cadherin by single-cell electroporation at the single-cell level. We found that pentylenetetrazol (PTZ) significantly enhanced the accumulation of N-cadherin in Mauthner axons, a response that was paralleled by enhanced sheath number per oligodendrocytes. By offsetting this phenotype using oligopeptide (AHAVD) which blocks the function of N-cadherin, we showed that PTZ regulates myelination in an N-cadherin-dependent manner. What is more, we further suggested that PTZ influences N-cadherin and myelination via a cAMP pathway. Consequently, our data indicated that N-cadherin is involved in neuronal activity-dependent regulation of myelinating capacity of zebrafish individual oligodendrocytes in vivo.

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Acknowledgments

We are grateful to David A. Lyons (University of Edinburgh) for plasmid (mbp-EGFP-CAAX) and Tg (mbp:mCherry-CAAX).

This research was supported by the National Natural Science Foundation of China (NSFC) 31571068,U1332136.

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Authors and Affiliations

  1. Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui Province, 230026, People’s Republic of China

    Min Chen, Yang Xu, Rongchen Huang, Shuchao Ge & Bing Hu

  2. Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People’s Republic of China

    Yubin Huang

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  1. Min Chen
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Correspondence to Bing Hu.

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All animal manipulations were conducted in strict accordance with the guidelines and regulations set forth by the University of Science and Technology of China (USTC) Animal Resources Center and University Animal Care and Use Committee. The protocol was approved by the Committee on the Ethics of Animal Experiments of the USTC (permit number: USTCACUC1103013).

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Chen, M., Xu, Y., Huang, R. et al. N-Cadherin is Involved in Neuronal Activity-Dependent Regulation of Myelinating Capacity of Zebrafish Individual Oligodendrocytes In Vivo. Mol Neurobiol 54, 6917–6930 (2017). https://doi.org/10.1007/s12035-016-0233-4

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