@article{9e06a8d4f286412a83b3a1eea0213230,
title = "Myelinating Schwann cells ensheath multiple axons in the absence of E3 ligase component Fbxw7",
abstract = "In the central nervous system (CNS), oligodendrocytes myelinate multiple axons; in the peripheral nervous system (PNS), Schwann cells (SCs) myelinate a single axon. Why are the myelinating potentials of these glia so fundamentally different? Here, we find that loss of Fbxw7, an E3 ubiquitin ligase component, enhances the myelinating potential of SCs. Fbxw7 mutant SCs make thicker myelin sheaths and sometimes appear to myelinate multiple axons in a fashion reminiscent of oligodendrocytes. Several Fbxw7 mutant phenotypes are due to dysregulation of mTOR; however, the remarkable ability of mutant SCs to ensheathe multiple axons is independent of mTOR signaling. This indicates distinct roles for Fbxw7 in SC biology including modes of axon interactions previously thought to fundamentally distinguish myelinating SCs from oligodendrocytes. Our data reveal unexpected plasticity in the myelinating potential of SCs, which may have important implications for our understanding of both PNS and CNS myelination and myelin repair.",
author = "Harty, {Breanne L.} and Fernanda Coelho and Pease-Raissi, {Sarah E.} and Amit Mogha and Ackerman, {Sarah D.} and Herbert, {Amy L.} and Gereau, {Robert W.} and Golden, {Judith P.} and Lyons, {David A.} and Chan, {Jonah R.} and Monk, {Kelly R.}",
note = "Funding Information: The authors thank the Monk lab (Washington University [WU] and the Vollum Institute at Oregon Health & Science University [OHSU]) for valuable discussions, as well as the Solnica-Krezel and Johnson laboratories (WU) for helpful feedback. The Cavalli Lab (WU), especially Dan Carlin, supplied helpful reagents and useful feedback. We also thank the Nechiporuk lab (OHSU) for helpful input and advice. We are indebted to Laura Feltri, Carmen Melendez-Vasquez, and Steve Scherer for helpful discussions and to Megan Corty and Ben Emery for critical comments on the paper. Electron microscopy was performed at the Multiscale Microscopy Core with technical support from the OHSU Center for Spatial Systems Biomedicine. Specifically, we thank Claudia Lopez, Jessica Riesterer, and Kevin Loftis for the help with imaging and analyzing the 3D SBF-SEM data. This work was supported by NIH/NINDS to B.L.H. (F31 NS094004); NIH/ NINDS to S.D.A. (F31 NS087801); NIH/NINDS to A.L.H. (F31 NS096814); NIH/NINDS to R.W.G. (R01 NS042595); NIH/NINDS to J.R.C. (R01NS062796); a Wellcome Senior Research Fellowship (D.A.L.), the Edward J. Mallinckrodt Jr. Foundation (K.R.M.), the Race to Erase MS Foundation (K.R.M.), and K.R.M. is a Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-10881-y",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}