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CNS myelin protein 36K regulates oligodendrocyte differentiation through Notch
Author(s) -
Nagarajan Bhuvaneswari,
Harder Alexander,
Japp Anna,
Häberlein Felix,
Mingardo Enrico,
Kleinert Henning,
Yilmaz Öznur,
Zoons Angelika,
Rau Birgit,
Christ Andrea,
Kubitscheck Ulrich,
Eiberger Britta,
Sandhoff Roger,
Eckhardt Matthias,
Hartmann Dieter,
Odermatt Benjamin
Publication year - 2020
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23732
Subject(s) - biology , notch signaling pathway , oligodendrocyte , microbiology and biotechnology , myelin , zebrafish , remyelination , myelin basic protein , central nervous system , neuroscience , signal transduction , biochemistry , gene
In contrast to humans and other mammals, zebrafish can successfully regenerate and remyelinate central nervous system (CNS) axons following injury. In addition to common myelin proteins found in mammalian myelin, 36K protein is a major component of teleost fish CNS myelin. Although 36K is one of the most abundant proteins in zebrafish brain, its function remains unknown. Here we investigate the function of 36K using translation‐blocking Morpholinos. Morphant larvae showed fewer dorsally migrated oligodendrocyte precursor cells as well as upregulation of Notch ligand. A gamma secretase inhibitor, which prevents activation of Notch, could rescue oligodendrocyte precursor cell numbers in 36K morphants, suggesting that 36K regulates initial myelination through inhibition of Notch signaling. Since 36K like other short chain dehydrogenases might act on lipids, we performed thin layer chromatography and mass spectrometry of lipids and found changes in lipid composition in 36K morphant larvae. Altogether, we suggest that during early development 36K regulates membrane lipid composition, thereby altering the amount of transmembrane Notch ligands and the efficiency of intramembrane gamma secretase processing of Notch and thereby influencing oligodendrocyte precursor cell differentiation and further myelination. Further studies on the role of 36K short chain dehydrogenase in oligodendrocyte precursor cell differentiation during remyelination might open up new strategies for remyelination therapies in human patients.