Journal Article

DZNE-2023-00152

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Myelination generates aberrant ultrastructure that is resolved by microglia.

Djannatian, M. (First author)DZNE* ; Radha, S.DZNE* ; Weikert, U. ; Safaiyani, S.DZNE* ; Wrede, C. ; Deichsel, C.DZNE* ; Kislinger, G.DZNE* ; Rhomberg, A. ; Ruhwedel, T. ; Campbell, D. S. ; van Ham, T. ; Schmid, B.DZNE* ; Hegermann, J. ; Möbius, W. ; Schifferer, M.DZNE* ; Simons, M.DZNE*

2023
Rockefeller Univ. Press New York, NY

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Please use a persistent id in citations: doi:10.1083/jcb.202204010  doi:10.60944/DZNE-2023-00152

Abstract: To enable rapid propagation of action potentials, axons are ensheathed by myelin, a multilayered insulating membrane formed by oligodendrocytes. Most of the myelin is generated early in development, resulting in the generation of long-lasting stable membrane structures. Here, we explored structural and dynamic changes in central nervous system myelin during development. To achieve this, we performed an ultrastructural analysis of mouse optic nerves by serial block face scanning electron microscopy (SBF-SEM) and confocal time-lapse imaging in the zebrafish spinal cord. We found that myelin undergoes extensive ultrastructural changes during early postnatal development. Myelin degeneration profiles were engulfed and phagocytosed by microglia using exposed phosphatidylserine as one 'eat me' signal. In contrast, retractions of entire myelin sheaths occurred independently of microglia and involved uptake of myelin by the oligodendrocyte itself. Our findings show that the generation of myelin early in development is an inaccurate process associated with aberrant ultrastructural features that require substantial refinement.

Keyword(s): Animals (MeSH) ; Mice (MeSH) ; Axons: ultrastructure (MeSH) ; Microglia: ultrastructure (MeSH) ; Myelin Sheath: ultrastructure (MeSH) ; Oligodendroglia: ultrastructure (MeSH) ; Zebrafish (MeSH) ; Optic Nerve: ultrastructure (MeSH) ; Microscopy, Electron, Scanning (MeSH) ; Phagocytosis (MeSH) ; Time-Lapse Imaging (MeSH)

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Contributing Institute(s):

1. Molecular Neurobiology (AG Simons)
2. Neuronal Cell Biology (AG Misgeld)
3. Fish Core Unit (AG Schmid)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

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Database coverage:
; ; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Green Open Access ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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