TY  - JOUR
AU  - Djannatian, Minou
AU  - Radha, Swathi
AU  - Weikert, Ulrich
AU  - Safaiyani, Shima
AU  - Wrede, Christoph
AU  - Deichsel, Cassandra
AU  - Kislinger, Georg
AU  - Rhomberg, Agata
AU  - Ruhwedel, Torben
AU  - Campbell, Douglas S
AU  - van Ham, Tjakko
AU  - Schmid, Bettina
AU  - Hegermann, Jan
AU  - Möbius, Wiebke
AU  - Schifferer, Martina
AU  - Simons, Mikael
TI  - Myelination generates aberrant ultrastructure that is resolved by microglia.
JO  - The journal of cell biology
VL  - 222
IS  - 3
SN  - 0021-9525
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - DZNE-2023-00152
SP  - e202204010
PY  - 2023
AB  - 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.
KW  - Animals
KW  - Mice
KW  - Axons: ultrastructure
KW  - Microglia: ultrastructure
KW  - Myelin Sheath: ultrastructure
KW  - Oligodendroglia: ultrastructure
KW  - Zebrafish
KW  - Optic Nerve: ultrastructure
KW  - Microscopy, Electron, Scanning
KW  - Phagocytosis
KW  - Time-Lapse Imaging
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9856851
C6  - pmid:36637807
DO  - DOI:10.1083/jcb.202204010
UR  - https://pub.dzne.de/record/169388
ER  -