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Precision in a sea of profusion: Myelin replacement triggered by single-cell cortical demyelination

Nicolas Snaidero, Martina Schifferer, Aleksandra Mezydlo, Martin Kerschensteiner, Thomas Misgeld
doi: https://doi.org/10.1101/2019.12.16.877597
Nicolas Snaidero
Institute of Neuronal Cell Biology, Technische Universität München, Munich, GermanyGerman Center for Neurodegenerative Diseases (DZNE), Munich, GermanyInstitute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians Universität München, Munich, GermanyBiomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians Universität München, Martinsried, Germany
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  • For correspondence: nicolas.snaidero@tum.de
Martina Schifferer
German Center for Neurodegenerative Diseases (DZNE), Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, Germany
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Aleksandra Mezydlo
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians Universität München, Munich, GermanyBiomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians Universität München, Martinsried, Germany
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Martin Kerschensteiner
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians Universität München, Munich, GermanyBiomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians Universität München, Martinsried, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, Germany
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Thomas Misgeld
Institute of Neuronal Cell Biology, Technische Universität München, Munich, GermanyGerman Center for Neurodegenerative Diseases (DZNE), Munich, GermanyMunich Cluster for Systems Neurology (SyNergy), Munich, Germany
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SUMMARY

Myelin—rather than being a static insulator of axons—is emerging as an active participant in circuit plasticity. This requires precise regulation of oligodendrocyte numbers and myelination patterns. Here, by devising a laser ablation approach of single oligodendrocytes, followed by in vivo imaging and correlated ultrastructural reconstruction, we show that in mouse cortex demyelination as subtle as loss of a single oligodendrocyte can trigger robust cell replacement and remyelination timed by myelin breakdown. This results in reliable reestablishment of the original myelin pattern along continuously myelinated axons, while in parallel profuse isolated internodes emerge on previously unmyelinated axons. Thus, in mammalian cortex, internodes along partially myelinated cortical axons are typically not re-established, suggesting that the cues that guide ‘patchy’ myelination are not preserved through cycles of de- and remyelination. In contrast, continuous ‘obligatory’ myelin shows remarkable homeostatic resilience with single axon precision.

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Posted December 17, 2019.
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Precision in a sea of profusion: Myelin replacement triggered by single-cell cortical demyelination
Nicolas Snaidero, Martina Schifferer, Aleksandra Mezydlo, Martin Kerschensteiner, Thomas Misgeld
bioRxiv 2019.12.16.877597; doi: https://doi.org/10.1101/2019.12.16.877597
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Precision in a sea of profusion: Myelin replacement triggered by single-cell cortical demyelination
Nicolas Snaidero, Martina Schifferer, Aleksandra Mezydlo, Martin Kerschensteiner, Thomas Misgeld
bioRxiv 2019.12.16.877597; doi: https://doi.org/10.1101/2019.12.16.877597

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