title: Mammalian target of rapamycin promotes oligodendrocyte differentiation, initiation and extent of CNS myelination.
abstract: Prior studies support a role for mammalian target of rapamycin (mTOR) signaling in oligodendrocyte differentiation and myelination. Here we use Cre-recombinase driven by the CNP promoter to generate a mouse line with oligodendrocyte-specific knockdown of mTOR (mTOR cKO) in the CNS. We provide evidence that mTOR is necessary for proper oligodendrocyte differentiation and myelination in the spinal cord. Specifically, the number of mature oligodendrocytes was reduced, and the initiation and extent of myelination were impaired during spinal cord development. Consistent with these data, myelin protein expression, including myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein, and myelin-associated glycoprotein, was delayed in the spinal cord. Hypomyelination of the spinal cord persisted into adulthood, as did the reduction in numbers of mature oligodendrocytes. In the cortex, the structure of myelin appeared normal during development and in the adult; however, myelin protein expression was delayed during development and was abnormal in the adult. Myelin basic protein was significantly reduced in all regions at postnatal day 25. These data demonstrate that mTOR promotes oligodendrocyte differentiation and CNS myelination in vivo and show that the requirement for mTOR varies by region with the spinal cord most dependent on mTOR.
authors.affiliation: Department of Neurology and Neuroscience, New Jersey Medical School Cancer Center, Rutgers Biomedical and Health Sciences, Newark, New Jersey 07103, and Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado 80045.
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Wahl
authors.forename: Lauren E
authors.initials: LE
authors.lastname: McLane
authors.forename: Kathryn K
authors.initials: KK
authors.lastname: Bercury
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Wood
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000235:genetics; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics*; D002490:Central Nervous System / Q000166:cytology* / Q000254:growth & development; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism* / Q000648:ultrastructure; D058570:TOR Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D009185:Myelin Proteins; D049452:Green Fluorescent Proteins; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; C045073:Cre recombinase; D019426:Integrases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571338:Cnp protein, mouse
keywords: differentiation; mTOR; myelination; oligodendrocyte; signaling