title: CNS myelin sheath is stochastically built by homotypic fusion of myelin membranes within the bounds of an oligodendrocyte process.
abstract: Myelin - the multilayer membrane that envelops axons - is a facilitator of rapid nerve conduction. Oligodendrocytes form CNS myelin; the prevailing hypothesis being that they do it by extending a process that circumnavigates the axon. It is pertinent to ask how myelin is built because oligodendrocyte plasma membrane and myelin are compositionally different. To this end, we examined oligodendrocyte cultures and embryonic avian optic nerves by electron microscopy, immuno-electron microscopy and three-dimensional electron tomography. The results support three novel concepts. Myelin membranes are synthesized as tubules and packaged into "myelinophore organelles" in the oligodendrocyte perikaryon. Myelin membranes are matured in and transported by myelinophore organelles within an oligodendrocyte process. The myelin sheath is generated by myelin membrane fusion inside an oligodendrocyte process. These findings abrogate the dogma of myelin resulting from a wrapping motion of an oligodendrocyte process and open up new avenues in the quest for understanding myelination in health and disease.
authors: Department of Neurology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: szuchet@neurology.bsd.uchicago.edu.
authors: Sara
authors: S
authors: Szuchet
authors: Department of Neurology, The University of Chicago, Chicago, IL 60637, USA.
authors: Lauren L
authors: LL
authors: Nielsen
authors: Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA.
authors: Miriam S
authors: MS
authors: Domowicz
authors: Advance Electron Microscopy Facility, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
authors: Jotham R
authors: JR
authors: Austin
authors: Department of Anatomy, Histology, Embryology, University of Thessaly, Larissa, Greece.
authors: Dimitrios L
authors: DL
authors: Arvanitis
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology; D002642:Chick Embryo; D009186:Myelin Sheath / Q000502:physiology / Q000648:ultrastructure*; D009836:Oligodendroglia / Q000502:physiology / Q000648:ultrastructure*; D015388:Organelles / Q000648:ultrastructure; D034561:Sheep, Domestic; D013269:Stochastic Processes
keywords: Axolemma; Glycolipid tubulation; Membrane curvature; Multiple sclerosis; Myelinogenesis; Oligodendrocyte plasma membrane