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Djannatian, Minou; Radha, Swathi; Weikert, Ulrich; Safaiyan, Shima; Wrede, Christoph; Deichsel, Cassandra; Kislinger, Georg; Rhomberg, Agata; Ruhwedel, Torben; Campbell, Douglas S.; van Ham, Tjakko; Schmid, Bettina; Hegermann, Jan; Moebius, Wiebke; Schifferer, Martina und Simons, Mikael (2023): Myelination generates aberrant ultrastructure that is resolved by microglia. In: Journal of Cell Biology, Bd. 222, Nr. 3, e202204010 [PDF, 6MB]

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. Djannatian et al. show by ultrastructural analysis of mouse optic nerves and in vivo imaging of zebrafish spinal cords that developmental myelination is an error-prone process and microglia contribute to the removal of aberrant structures. This may be an important mechanism to generate properly functioning myelin.

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