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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-08, Vol.112 (33), p.10509-10514
Main Authors: Mills, Elizabeth A, Davis, Chung-ha O, Bushong, Eric A, Boassa, Daniela, Kim, Keun-Young, Ellisman, Mark H, Marsh-Armstrong, Nicholas
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Antigens, Surface - metabolism
Astrocytes - cytology
Axons - metabolism
Biological Sciences
Developmental biology
Frogs
Immunohistochemistry
Lipids - chemistry
Membranes
Metamorphosis, Biological
Microglia - metabolism
Microscopy, Electron
Microscopy, Electron, Transmission
Myelin Sheath - chemistry
Nerve Regeneration
Optic nerve
Optic Nerve - physiology
Pathology
Phagocytes - cytology
Phagocytosis - physiology
rac1 GTP-Binding Protein - physiology
Time Factors
Transgenes
Triiodothyronine - genetics
Xenopus laevis
Xenopus laevis - physiology
Xenopus Proteins - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1506486112