Astrocytes phagocytose focal dystrophies from shortening myelin segments in the optic nerve of Xenopus laevis at metamorphosis

Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10509-14. doi: 10.1073/pnas.1506486112. Epub 2015 Aug 3.

Abstract

Oligodendrocytes can adapt to increases in axon diameter through the addition of membrane wraps to myelin segments. Here, we report that myelin segments can also decrease their length in response to optic nerve (ON) shortening during Xenopus laevis metamorphic remodeling. EM-based analyses revealed that myelin segment shortening is accomplished by focal myelin-axon detachments and protrusions from otherwise intact myelin segments. Astrocyte processes remove these focal myelin dystrophies using known phagocytic machinery, including the opsonin milk fat globule-EGF factor 8 (Mfge8) and the downstream effector ras-related C3 botulinum toxin substrate 1 (Rac1). By the end of metamorphic nerve shortening, one-quarter of all myelin in the ON is enwrapped or internalized by astrocytes. As opposed to the removal of degenerating myelin by macrophages, which is usually associated with axonal pathologies, astrocytes selectively remove large amounts of myelin without damaging axons during this developmental remodeling event.

Keywords: Mfge8; glia; lipid droplet; thyroid hormone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antigens, Surface / metabolism
  • Astrocytes / cytology*
  • Axons / metabolism
  • Immunohistochemistry
  • Lipids / chemistry
  • Metamorphosis, Biological
  • Microglia / metabolism
  • Microscopy, Electron
  • Microscopy, Electron, Transmission
  • Myelin Sheath / chemistry*
  • Nerve Regeneration
  • Optic Nerve / physiology*
  • Phagocytes / cytology
  • Phagocytosis / physiology*
  • Time Factors
  • Transgenes
  • Triiodothyronine / genetics
  • Xenopus Proteins / metabolism
  • Xenopus laevis / physiology*
  • rac1 GTP-Binding Protein / physiology

Substances

  • Antigens, Surface
  • Lipids
  • MFGE8 protein, Xenopus
  • Xenopus Proteins
  • Triiodothyronine
  • rac1 GTP-Binding Protein