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.thyroid hormone | glia | lipid droplet | Mfge8 M yelin exists as regularly spaced segments that enable fast and efficient transfer of information across long distances through saltatory propagation of action potentials between nodes of Ranvier (1). The number, length, and thickness of individual segments vary with species and nervous system region (2). The proper thickness and length of myelin segments are likely established, at least in part, during the myelination process itself, which involves the dynamic elongation, shortening, and removal of individual segments (3, 4). However, once established, some myelin segments must be modified further to accommodate axonal growth. Developmental increases in axon diameter are coupled to the addition of membrane wraps to myelin segments, thereby maintaining a near-linear relationship between axon caliber and myelin thickness (5, 6). In the peripheral nervous system, Schwann cell myelin segments can also elongate in proportion to nerve length, increasing internodal distances by as much as a factor of four (3, 7). The regulation of myelin on axons is essential for the proper function of the vertebrate nervous system, because both hypomyelination and hypermyelination lead to neuropathy (8). However, the mechanisms involved in myelin segment plasticity have remained poorly understood, in part, because of the difficulty in studying a process that occurs in mammals during a protracted period as the animals mature (2).During metamorphic remodeling of the head in Xenopus laevis, the optic nerve (ON) and its associated axons rapidly shorten in length (9). A description of this process (10) noted abnormally folded myelin on axons and membranous material inside glial cells, suggesting that myelin might be remodeling, thereby providing a model system in which to study myelin plasticity. The current study set out to determine how myelin segments remodel during ON shortening.
Results
The ON and Its Myelinated Axons Widen and Shorten During X. laevisMetamorphosis. The head of ...