Gas6 enhances axonal ensheathment by MBP+ membranous processes in human DRG/OL promyelinating co-cultures

Kathleen N. O'Guin, Ross C. Gruber, Cedric S. Raine, Hillary M. Guzik, Bradford K. Poulos, Bridget Shafit-Zagardo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The molecular requirements for human myelination are incompletely defined, and further study is needed to fully understand the cellular mechanisms involved during development and in demyelinating diseases. We have established a human co-culture model to study myelination. Our earlier observations showed that addition of human γ-carboxylated growth-arrest-specific protein 6 (Gas6) to human oligodendrocyte progenitor cell (OPC) cultures enhanced their survival and maturation. Therefore, we explored the effect of Gas6 in co-cultures of enriched OPCs plated on axons of human fetal dorsal root ganglia explant. Gas6 significantly enhanced the number of myelin basic protein-positive (MBP+) oligodendrocytes with membranous processes parallel with and ensheathing axons relative to co-cultures maintained in defined medium only for 14 days. Gas6 did not increase the overall number ofMBP+ oligodendrocytes/culture; however, it significantly increased the length of MBP+ oligodendrocyte processes in contact with and wrapping axons. Multiple oligodendrocytes were in contactwith a single axon, and several processes from one oligodendrocyte made contact with one or multiple axons. Electronmicroscopy supported confocal Z-seriesmicroscopy demonstrating axonal ensheathment by MBP+ oligodendrocyte membranous processes in Gas6treated co-cultures. Contacts between the axonal and oligodendrocyte membranes were evident and multiple wraps of oligodendrocyte membrane around the axon were visible supporting a model system in which to study events in human myelination and aspects of non-compact myelin formation. 2014 The Author(s).

Original languageEnglish (US)
Pages (from-to)29-42
Number of pages14
JournalASN Neuro
Volume6
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Growth arrest-specific protein 6
  • Human OPC/DRG co-culture
  • Myelination
  • Oligodendrocyte

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology

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