title: Neuronal activity biases axon selection for myelination in vivo.
abstract: An essential feature of vertebrate neural development is ensheathment of axons with myelin, an insulating membrane formed by oligodendrocytes. Not all axons are myelinated, but mechanisms directing myelination of specific axons are unknown. Using zebrafish, we found that activity-dependent secretion stabilized myelin sheath formation on select axons. When VAMP2-dependent exocytosis was silenced in single axons, oligodendrocytes preferentially ensheathed neighboring axons. Nascent sheaths formed on silenced axons were shorter in length, but when activity of neighboring axons was also suppressed, inhibition of sheath growth was relieved. Using in vivo time-lapse microscopy, we found that only 25% of oligodendrocyte processes that initiated axon wrapping were stabilized during normal development and that initiation did not require activity. Instead, oligodendrocyte processes wrapping silenced axons retracted more frequently. We propose that axon selection for myelination results from excessive and indiscriminate initiation of wrapping followed by refinement that is biased by activity-dependent secretion from axons.
authors: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors: Jacob H
authors: JH
authors: Hines
authors: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors: Andrew M
authors: AM
authors: Ravanelli
authors: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors: Rani
authors: R
authors: Schwindt
authors: School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
authors: Ethan K
authors: EK
authors: Scott
authors: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors: Bruce
authors: B
authors: Appel
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure*; D005089:Exocytosis / Q000187:drug effects; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics; D018613:Microscopy, Confocal; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis; D009836:Oligodendroglia / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D059008:Time-Lapse Imaging; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics; D014701:Veratridine / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology
chemical_list: D018398:Homeodomain Proteins; C489457:KCNJ2 protein, human; C109220:NBPhox protein; D024661:Potassium Channels, Inwardly Rectifying; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D014701:Veratridine