A neuronal PI(3,4,5)P 3 -dependent program of oligodendrocyte precursor recruitment and myelination

• Published in: Nature neuroscience Vol. 20; no. 1; p. 10
• Main Authors: Goebbels, Sandra, Wieser, Georg L, Pieper, Alexander, Spitzer, Sonia, Weege, Bettina, Yan, Kuo, Edgar, Julia M, Yagensky, Oleksandr, Wichert, Sven P, Agarwal, Amit, Karram, Khalad, Renier, Nicolas, Tessier-Lavigne, Marc, Rossner, Moritz J, Káradóttir, Ragnhildur Thóra, Nave, Klaus-Armin
• Format: Journal Article
• Language: English
• Published: United States 01-01-2017
• Subjects: Animals; Axons - metabolism; Cell Differentiation - genetics; Cell Differentiation - physiology; Mice, Transgenic; Myelin Sheath - metabolism; Nerve Tissue Proteins - metabolism; Neurons - metabolism; Oligodendroglia - cytology; Phosphatidylinositols - metabolism
• ISSN: 1546-1726
• DOI: 10.1038/nn.4425

The molecular trigger of CNS myelination is unknown. By targeting Pten in cerebellar granule cells and activating the AKT1-mTOR pathway, we increased the caliber of normally unmyelinated axons and the expression of numerous genes encoding regulatory proteins. This led to the expansion of genetically wild-type oligodendrocyte progenitor cells, oligodendrocyte differentiation and de novo myelination of parallel fibers. Thus, a neuronal program dependent on the phosphoinositide PI(3,4,5)P
is sufficient to trigger all steps of myelination.