title: Astrocytes phagocytose focal dystrophies from shortening myelin segments in the optic nerve of Xenopus laevis at metamorphosis.
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.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mills
authors.affiliation: Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Baltimore, MD 21205;
authors.forename: Chung-ha O
authors.initials: CH
authors.lastname: Davis
authors.affiliation: National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California at San Diego, La Jolla, CA 92093;
authors.forename: Eric A
authors.identifier: http://orcid.org/0000-0001-6195-2433
authors.initials: EA
authors.lastname: Bushong
authors.affiliation: National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California at San Diego, La Jolla, CA 92093;
authors.forename: Daniela
authors.initials: D
authors.lastname: Boassa
authors.affiliation: National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California at San Diego, La Jolla, CA 92093;
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Kim
authors.affiliation: National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California at San Diego, La Jolla, CA 92093; Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205; Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Baltimore, MD 21205; marsh-armstrong@jhmi.edu.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Marsh-Armstrong
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000954:Antigens, Surface / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology*; D001369:Axons / Q000378:metabolism; D007150:Immunohistochemistry; D008055:Lipids / Q000737:chemistry; D008675:Metamorphosis, Biological; D017628:Microglia / Q000378:metabolism; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000737:chemistry*; D009416:Nerve Regeneration; D009900:Optic Nerve / Q000502:physiology*; D010586:Phagocytes / Q000166:cytology; D010587:Phagocytosis / Q000502:physiology*; D013997:Time Factors; D019076:Transgenes; D014284:Triiodothyronine / Q000235:genetics; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology
chemical_list: D000954:Antigens, Surface; D008055:Lipids; C000602977:MFGE8 protein, Xenopus; D029867:Xenopus Proteins; D014284:Triiodothyronine; D020830:rac1 GTP-Binding Protein
keywords: Mfge8; glia; lipid droplet; thyroid hormone