{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:44:09Z","timestamp":1792122249243,"version":"4.4.0"},"reference-count":78,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T00:00:00Z","timestamp":1504742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T00:00:00Z","timestamp":1504742400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T00:00:00Z","timestamp":1504742400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["Marie Curie Actions Intra-European Fellowship"],"award-info":[{"award-number":["Marie Curie Actions Intra-European Fellowship"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Myelination is a biosynthetically demanding process in which mTORC1, the gatekeeper of anabolism, occupies a privileged regulatory position. We have shown previously that loss of mTORC1 function in Schwann cells (SCs) hampers myelination. Here, we genetically disrupted key inhibitory components upstream of mTORC1, TSC1 or PTEN, in mouse SC development, adult homeostasis, and nerve injury. Surprisingly, the resulting mTORC1 hyperactivity led to markedly delayed onset of both developmental myelination and remyelination after injury. However, if mTORC1 was hyperactivated after myelination onset, radial hypermyelination was observed. At early developmental stages, physiologically high PI3K-Akt-mTORC1 signaling suppresses expression of Krox20 (Egr2), the master regulator of PNS myelination. This effect is mediated by S6K and contributes to control mechanisms that keep SCs in a not-fully differentiated state to ensure proper timing of myelination initiation. An ensuing decline in mTORC1 activity is crucial to allow myelination to start, while remaining mTORC1 activity drives myelin growth.<\/jats:p>","DOI":"10.7554\/elife.29241","type":"journal-article","created":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T01:00:10Z","timestamp":1504659610000},"source":"Crossref","is-referenced-by-count":99,"title":["Dual function of the PI3K-Akt-mTORC1 axis in myelination of the peripheral nervous system"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8689-8488","authenticated-orcid":true,"given":"Gianluca","family":"Figlia","sequence":"first","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Norrm\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge A","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gerber","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9211-5184","authenticated-orcid":true,"given":"Ueli","family":"Suter","sequence":"additional","affiliation":[{"name":"Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2017,9,7]]},"reference":[{"key":"bib1","doi-asserted-by":"crossref","first-page":"7891","DOI":"10.1523\/JNEUROSCI.18-19-07891.1998","article-title":"Promyelinating Schwann cells express Tst-1\/SCIP\/Oct-6","volume":"18","author":"Arroyo","year":"1998","journal-title":"Journal of Neuroscience"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"E4261","DOI":"10.1073\/pnas.1620761114","article-title":"mTORC1 promotes proliferation of immature Schwann cells and myelin growth of differentiated Schwann cells","volume":"114","author":"Beirowski","year":"2017","journal-title":"PNAS"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1126\/science.1228792","article-title":"Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1","volume":"339","author":"Ben-Sahra","year":"2013","journal-title":"Science"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1126\/science.aad0489","article-title":"mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle","volume":"351","author":"Ben-Sahra","year":"2016","journal-title":"Science"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.cmet.2008.10.002","article-title":"Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy","volume":"8","author":"Bentzinger","year":"2008","journal-title":"Cell Metabolism"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"4466","DOI":"10.1523\/JNEUROSCI.4314-13.2014","article-title":"Conditional ablation of raptor or rictor has differential impact on oligodendrocyte differentiation and CNS myelination","volume":"34","author":"Bercury","year":"2014","journal-title":"Journal of Neuroscience"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.15252\/emmm.201606349","article-title":"Niacin-mediated Tace activation ameliorates CMT neuropathies with focal hypermyelination","volume":"8","author":"Bolino","year":"2016","journal-title":"EMBO Molecular Medicine"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"2834","DOI":"10.1038\/ncomms3834","article-title":"The TSC-mTOR pathway regulates macrophage polarization","volume":"4","author":"Byles","year":"2013","journal-title":"Nature Communications"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1172\/JCI84262","article-title":"Tuberous sclerosis complex inactivation disrupts melanogenesis via mTORC1 activation","volume":"127","author":"Cao","year":"2017","journal-title":"Journal of Clinical Investigation"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"3065","DOI":"10.1172\/JCI34739","article-title":"Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer","volume":"118","author":"Carracedo","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.cmet.2013.03.015","article-title":"Sustained activation of mTORC1 in skeletal muscle inhibits constitutive and starvation-induced autophagy and causes a severe, late-onset myopathy","volume":"17","author":"Castets","year":"2013","journal-title":"Cell Metabolism"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1146\/annurev.neuro.30.051606.094337","article-title":"Peripheral regeneration","volume":"30","author":"Chen","year":"2007","journal-title":"Annual Review of Neuroscience"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1194\/jlr.R009761","article-title":"Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models","volume":"52","author":"Chrast","year":"2011","journal-title":"Journal of Lipid Research"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1126\/science.1187735","article-title":"Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination","volume":"328","author":"Cotter","year":"2010","journal-title":"Science"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.molcel.2012.06.009","article-title":"TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1","volume":"47","author":"Dibble","year":"2012","journal-title":"Molecular Cell"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"4506","DOI":"10.1523\/JNEUROSCI.3521-15.2016","article-title":"Akt Regulates Axon Wrapping and Myelin Sheath Thickness in the PNS","volume":"36","author":"Dom\u00e8nech-Est\u00e9vez","year":"2016","journal-title":"Journal of Neuroscience"},{"key":"bib18","volume-title":"Peripheral Neuropathy","author":"Dyck","year":"2005"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.ceb.2009.10.007","article-title":"mTOR and cancer: many loops in one pathway","volume":"22","author":"Efeyan","year":"2010","journal-title":"Current Opinion in Cell Biology"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/j.1749-6632.1999.tb08574.x","article-title":"P0-Cre transgenic mice for inactivation of adhesion molecules in Schwann cells","volume":"883","author":"Feltri","year":"1999","journal-title":"Annals of the New York Academy of Sciences"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1177\/1073858415572361","article-title":"How Schwann Cells Sort Axons: New Concepts","volume":"22","author":"Feltri","year":"2016","journal-title":"The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1038\/nm.3664","article-title":"Soluble neuregulin-1 modulates disease pathogenesis in rodent models of Charcot-Marie-Tooth disease 1A","volume":"20","author":"Fledrich","year":"2014","journal-title":"Nature Medicine"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"7174","DOI":"10.1523\/JNEUROSCI.0150-08.2008","article-title":"Constitutively active Akt induces enhanced myelination in the CNS","volume":"28","author":"Flores","year":"2008","journal-title":"Journal of Neuroscience"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"e2001408","DOI":"10.1371\/journal.pbio.2001408","article-title":"Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination","volume":"15","author":"Ghidinelli","year":"2017","journal-title":"PLoS Biology"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"8953","DOI":"10.1523\/JNEUROSCI.0219-10.2010","article-title":"Elevated phosphatidylinositol 3,4,5-trisphosphate in glia triggers cell-autonomous membrane wrapping and myelination","volume":"30","author":"Goebbels","year":"2010","journal-title":"Journal of Neuroscience"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/emmm.201200227","article-title":"Genetic disruption of Pten in a novel mouse model of tomaculous neuropathy","volume":"4","author":"Goebbels","year":"2012","journal-title":"EMBO Molecular Medicine"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"R29","DOI":"10.1016\/j.cub.2006.11.042","article-title":"Rapid conduction and the evolution of giant axons and myelinated fibers","volume":"17","author":"Hartline","year":"2007","journal-title":"Current Biology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1101\/gad.1212704","article-title":"Upstream and downstream of mTOR","volume":"18","author":"Hay","year":"2004","journal-title":"Genes & Development"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1083\/jcb.201307057","article-title":"Functionally distinct PI 3-kinase pathways regulate myelination in the peripheral nervous system","volume":"204","author":"Heller","year":"2014","journal-title":"The Journal of Cell Biology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.conb.2016.11.003","article-title":"Advances in myelinating glial cell development","volume":"42","author":"Herbert","year":"2017","journal-title":"Current Opinion in Neurobiology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"12509","DOI":"10.1074\/jbc.M110.200543","article-title":"WIPI1 coordinates melanogenic gene transcription and melanosome formation via TORC1 inhibition","volume":"286","author":"Ho","year":"2011","journal-title":"Journal of Biological Chemistry"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/ncb839","article-title":"TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling","volume":"4","author":"Inoki","year":"2002","journal-title":"Nature Cell Biology"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/ng1494","article-title":"Dysregulation of the TSC-mTOR pathway in human disease","volume":"37","author":"Inoki","year":"2005","journal-title":"Nature Genetics"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1523\/JNEUROSCI.4403-12.2013","article-title":"Sustained activation of ERK1\/2 MAPK in oligodendrocytes and schwann cells enhances myelin growth and stimulates oligodendrocyte progenitor expansion","volume":"33","author":"Ishii","year":"2013","journal-title":"Journal of Neuroscience"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1101\/gad.258203","article-title":"The POU proteins Brn-2 and Oct-6 share important functions in Schwann cell development","volume":"17","author":"Jaegle","year":"2003","journal-title":"Genes & Development"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.1113\/JP270874","article-title":"The repair Schwann cell and its function in regenerating nerves","volume":"594","author":"Jessen","year":"2016","journal-title":"The Journal of Physiology"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"12185","DOI":"10.1038\/ncomms12185","article-title":"Regulation of PERK-eIF2\u03b1 signalling by tuberous sclerosis complex-1 controls homoeostasis and survival of myelinating oligodendrocytes","volume":"7","author":"Jiang","year":"2016","journal-title":"Nature Communications"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1093\/hmg\/11.5.525","article-title":"A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells","volume":"11","author":"Kwiatkowski","year":"2002","journal-title":"Human Molecular Genetics"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"8432","DOI":"10.1523\/JNEUROSCI.1105-14.2014","article-title":"Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination","volume":"34","author":"Lebrun-Julien","year":"2014","journal-title":"Journal of Neuroscience"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/S1044-7431(03)00029-0","article-title":"Tamoxifen-inducible glia-specific Cre mice for somatic mutagenesis in oligodendrocytes and Schwann cells","volume":"22","author":"Leone","year":"2003","journal-title":"Molecular and Cellular Neuroscience"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.08.053","article-title":"The regulation of cell size","volume":"154","author":"Lloyd","year":"2013","journal-title":"Cell"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S1097-2765(02)00568-3","article-title":"Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase\/akt pathway","volume":"10","author":"Manning","year":"2002","journal-title":"Molecular Cell"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"7628","DOI":"10.1523\/JNEUROSCI.0726-16.2016","article-title":"Cholesterol biosynthesis supports myelin gene expression and axon ensheathment through modulation of P13K\/Akt\/mTor signaling","volume":"36","author":"Mathews","year":"2016","journal-title":"Journal of Neuroscience"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.neuron.2014.06.007","article-title":"Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases","volume":"83","author":"Mei","year":"2014","journal-title":"Neuron"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1002\/glia.22852","article-title":"New insights on Schwann cell development","volume":"63","author":"Monk","year":"2015","journal-title":"Glia"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.devcel.2015.05.013","article-title":"Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system","volume":"34","author":"Nawaz","year":"2015","journal-title":"Developmental Cell"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/emmm.201100131","article-title":"Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis","volume":"3","author":"Neuman","year":"2011","journal-title":"EMBO Molecular Medicine"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.neuron.2010.12.003","article-title":"Specific functions for ERK\/MAPK signaling during PNS development","volume":"69","author":"Newbern","year":"2011","journal-title":"Neuron"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.nbd.2014.06.023","article-title":"Rapamycin improves peripheral nerve myelination while it fails to benefit neuromuscular performance in neuropathic mice","volume":"70","author":"Nicks","year":"2014","journal-title":"Neurobiology of Disease"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.celrep.2014.09.001","article-title":"mTORC1 controls PNS myelination along the mTORC1-RXR\u03b3-SREBP-lipid biosynthesis axis in Schwann cells","volume":"9","author":"Norrm\u00e9n","year":"2014","journal-title":"Cell Reports"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1111\/j.1471-4159.1973.tb07520.x","article-title":"Myelination in rat brain: changes in myelin composition during brain maturation","volume":"21","author":"Norton","year":"1973","journal-title":"Journal of Neurochemistry"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1083\/jcb.201010013","article-title":"N-WASP is required for membrane wrapping and myelination by Schwann cells","volume":"192","author":"Novak","year":"2011","journal-title":"The Journal of Cell Biology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.tins.2011.11.006","article-title":"Molecular mechanisms regulating myelination in the peripheral nervous system","volume":"35","author":"Pereira","year":"2012","journal-title":"Trends in Neurosciences"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.cmet.2008.09.003","article-title":"Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration","volume":"8","author":"Polak","year":"2008","journal-title":"Cell Metabolism"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.cmet.2008.07.007","article-title":"SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth","volume":"8","author":"Porstmann","year":"2008","journal-title":"Cell Metabolism"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1073\/pnas.96.5.2110","article-title":"Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase\/Akt pathway","volume":"96","author":"Ramaswamy","year":"1999","journal-title":"PNAS"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.molcel.2007.03.003","article-title":"PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase","volume":"25","author":"Sancak","year":"2007","journal-title":"Molecular Cell"},{"key":"bib60","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1523\/JNEUROSCI.14-04-01930.1994","article-title":"Axons regulate Schwann cell expression of the POU transcription factor SCIP","volume":"14","author":"Scherer","year":"1994","journal-title":"Journal of Neuroscience"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1101\/gad.230045.113","article-title":"Activation of MAPK overrides the termination of myelin growth and replaces Nrg1\/ErbB3 signals during Schwann cell development and myelination","volume":"28","author":"Sheean","year":"2014","journal-title":"Genes & Development"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1523\/JNEUROSCI.4814-11.2012","article-title":"Arrest of myelination and reduced axon growth when Schwann cells lack mTOR","volume":"32","author":"Sherman","year":"2012","journal-title":"Journal of Neuroscience"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/nrm3330","article-title":"The functions and regulation of the PTEN tumour suppressor","volume":"13","author":"Song","year":"2012","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1002\/glia.20767","article-title":"The molecular machinery of myelin gene transcription in Schwann cells","volume":"56","author":"Svaren","year":"2008","journal-title":"Glia"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"ra18","DOI":"10.1126\/scisignal.2004809","article-title":"mTORC1 promotes denervation-induced muscle atrophy through a mechanism involving the activation of FoxO and E3 ubiquitin ligases","volume":"7","author":"Tang","year":"2014","journal-title":"Science Signaling"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.conb.2016.03.006","article-title":"Schwann cells-axon interaction in myelination","volume":"39","author":"Taveggia","year":"2016","journal-title":"Current Opinion in Neurobiology"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1016\/S0960-9822(03)00506-2","article-title":"Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb","volume":"13","author":"Tee","year":"2003","journal-title":"Current Biology"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nature11083","article-title":"A unifying model for mTORC1-mediated regulation of mRNA translation","volume":"485","author":"Thoreen","year":"2012","journal-title":"Nature"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/371796a0","article-title":"Krox-20 controls myelination in the peripheral nervous system","volume":"371","author":"Topilko","year":"1994","journal-title":"Nature"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/ncb1547","article-title":"Insulin signalling to mTOR mediated by the Akt\/PKB substrate PRAS40","volume":"9","author":"Vander Haar","year":"2007","journal-title":"Nature Cell Biology"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"4453","DOI":"10.1523\/JNEUROSCI.4311-13.2014","article-title":"Mammalian target of rapamycin promotes oligodendrocyte differentiation, initiation and extent of CNS myelination","volume":"34","author":"Wahl","year":"2014","journal-title":"Journal of Neuroscience"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1002\/mus.880030207","article-title":"Determinants of conduction velocity in myelinated nerve fibers","volume":"3","author":"Waxman","year":"1980","journal-title":"Muscle & Nerve"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1083\/jcb.48.2.348","article-title":"The geometry of peripheral myelin sheaths during their formation and growth in rat sciatic nerves","volume":"48","author":"Webster","year":"1971","journal-title":"The Journal of Cell Biology"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"e00108","DOI":"10.1042\/AN20120092","article-title":"mTOR: a link from the extracellular milieu to transcriptional regulation of oligodendrocyte development","volume":"5","author":"Wood","year":"2013","journal-title":"ASN Neuro"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.cmet.2011.06.002","article-title":"Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways","volume":"14","author":"Yecies","year":"2011","journal-title":"Cell Metabolism"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1006\/mcne.1996.0052","article-title":"The transcription factors SCIP and Krox-20 mark distinct stages and cell fates in Schwann cell differentiation","volume":"8","author":"Zorick","year":"1996","journal-title":"Molecular and Cellular Neuroscience"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"15764","DOI":"10.1523\/JNEUROSCI.2267-14.2014","article-title":"Oligodendrocyte precursor cell-intrinsic effect of Rheb1 controls differentiation and mediates mTORC1-dependent myelination in brain","volume":"34","author":"Zou","year":"2014","journal-title":"Journal of Neuroscience"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.devcel.2015.06.011","article-title":"CNS myelin wrapping is driven by actin disassembly","volume":"34","author":"Zuchero","year":"2015","journal-title":"Developmental Cell"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/29241\/elife-29241-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/29241\/elife-29241-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/29241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:58:54Z","timestamp":1697057934000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/29241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,7]]},"references-count":78,"alternative-id":["10.7554\/eLife.29241"],"URL":"https:\/\/doi.org\/10.7554\/elife.29241","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"uri","id":"http:\/\/www.ebi.ac.uk\/ena\/data\/view\/PRJEB20661","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.29241.035","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.29241.034","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,7]]},"article-number":"e29241"}}