The Structure of Myelin Sheaths in the Central Nervous System of Xenopus laevis (Daudin)

The structure of myelinated nerve fibres has been studied in the spinal cord and optic nerve of the tadpoles of Xenopus laevis. Potassium permanganate-fixed material was examined with the electron microscope. The myelin sheath itself is made up of spirally arranged lamellae in which the intraperiod and dense lines alternate. Inside the myelin sheath an inner cytoplasmic process surrounds the axon and where the external surfaces of its bounding membrane come together an internal mesaxon is formed. The intraperiod line begins within the mesaxon and the dense line usually begins in the same region by apposition of the cytoplasmic surfaces of the membrane. The width of each lamella is 140 A. The outer line in the sheath is the dense line and this terminates in a tongue where the cytoplasmic surfaces of the myelin-forming glial cell separate. Thus, central myelin in Xenopus tadpoles is arranged in the same way as peripheral myelin, the only difference being that in central fibres, cytoplasm on the outside of the sheath is confined to that present in the tongue. For this reason adjacent central sheaths come into apposition without any intervening material being present. When this occurs an intraperiod line is formed between them.     

P0 promoter directs expression of reporter and toxin genes to Schwann cells of transgenic mice.

We generated transgenic mice that specifically express foreign genes in myelinating Schwann cells. A 1.1 kb segment of 5' flanking sequence from the rat P0 gene was used to drive expression of the genes encoding human growth hormone (hGH) and bacterial diphtheria toxin A chain (DT-A). The P0-hGH mice expressed hGH in myelinating Schwann cells, but not in nonmyelinating Schwann cells, the central nervous system, or any other tissue assayed. This expression was activated on a developmental schedule comparable to that of endogenous myelin gene expression. One line of P0-DT-A mice developed a generalized hypomyelinating peripheral neuropathy, with Schwann cell deficiency apparent in newborn animals. Peripheral nerves from adult mice of this line displayed morphological alterations ranging from completely denuded axons to myelinated Schwann cells undergoing degeneration, although occasional Schwann cells were able to form apparently normal myelin sheaths. Pronounced secondary changes, including proliferation and retraction of processes, occurred in the nonmyelinating Schwann cells of these P0-DT-A mice.     

Ultrastructural sequence of myelin breakdown during Wallerian degeneration in the rat optic nerve

Summary Adult albino rats were subjected to unilateral surgical removal of the eyeball. After survival times of 7–140 days, the numerical response of the neuroglial cells, and the progressive disintegration of the myelin sheaths in the optic nerves, were studied qualitatively and quantitatively in electron-microscopic montages. The distribution density of microglia and astroglia in degenerating optic nerve increased to peaks after 35 and 56 days respectively, whereas, the oligodendroglia gradually decreased. During the early stage of degeneration, microglial cells appeared and invaded the sheath at the intraperiod line, peeling off the outer lamellae, which were then engulfed by phagocytosis. Within the microglia, myelin sheath fragments were surrounded by a membrane curled to form a myelin ring. In the intermediate stage of degeneration, the paired electrondense lines of the ring, made up of myelin basic protein, decomposed and formed a homogenous or heterogenous osmiophilic layered structure, the myelin body, which, in the final stages, disintegrated and transformed into globoid lipid droplets and needle shaped cholesterol crystals.     

Progressive white matter pathology in the spinal cord of transgenic mice expressing mutant (P301L) human tau

Transgenic mice expressing mutant (P301L) tau develop paresis, neurofibrillary tangles and neuronal loss in spinal motor neurons beginning at 4 to 6 months of age. Astrocytes and oligodendrocytes acquire filamentous tau inclusions at later ages. Here we report pathology in the spinal white matter of these animals. Progressive white matter pathology, detected as early as 2 months of age, was most marked in lateral and anterior columns, with sparing of posterior columns until late in the disease. Early changes in Luxol fast blue/periodic acid Schiff (LFB/PAS) and toluidine blue stained sections were vacuolation of myelin followed by accumulation of myelin figures within previous axonal tubes and finally influx of PAS-positive macrophages. Myelin debris and vacuoles were found in macrophages. At the ultrastructural level, myelinated axons showed extensive vacuolation of myelin sheaths formed by splitting of myelin lamellae at the intra-period line, while axons were atrophic and contained densely packed neurofilaments. Other axons were lost completely, resulting in collapse and phagocytosis of myelin sheaths. Also present were spheroids derived from swollen axons with thin myelin sheaths containing neurofilaments, tau filaments and degenerating organelles. Many oligodendrocytes had membrane-bound cytoplasmic bodies composed of tightly stacked lamellae capped by dense material. The vacuolar myelopathy in this model to some extent resembles that reported in acquired immune deficiency syndrome and vitamin B12 deficiency. The progressive axonal pathology is most consistent with a dying-back process caused by abnormal accumulation of tau in upstream neurons, while vacuolar myelinopathy may be a secondary manifestation of neuroinflammation.     

Demyelination and cytopathic effects in cultures of mammalian dorsal root ganglia infected with encephalomyocarditis virus.

Replication of encephalomyocarditis virus and its cytopathic effects were studied in myelinated cultures of dorsal root ganglia obtained from newborn mice. Six hours after infection virus progeny was detected in the culture. At 24 h the virus titer reached 2 times 10(6) PFU per culture and remained at this level until 48 h. The first cytopathic alterations began at 24 h and consisted of rounding of Schwann and satellites cells and their detachment from neurons. Later, bead-like swellings of the myelin appeared along the axons followed by splitting and degeneration of lamellae. The cytopathic effect in the neurons started 29 h after infection, reaching complete neuronolysis at 48 h. Virus particles, scattered or arranged in crystal-like aggregates, were first seen in the cytoplasm of glial cells and then in neurons and axons.     

Alteration of ethanolamine glycerophospholipid turnover in trembler dysmyelinating mutant: An analysis of the sciatic nerve by biochemistry and radioautography

The turnover of phospholipids was compared in peripheral nerves of Trembler dysmelinating mutant and control mice, after intraperitoneal and local injection of labeled ethanolamine. In the mutant sciatic nerve, neurochemical analysis showed that [¹⁴C]ethanolamine is incorporated into EGP (ethanolamine glycerophospholipids) of the sciatic nerve at a much higher rate in Trembler mutant than in control mice. Furthermore the decay rate of ¹⁴C-labeled EGP is faster in Trembler than in normal animals. The accelerated turnover of EGP in Trembler sciatic nerve affects the diacyl-EGP while the renewal of the alkenylacyl-EGP (plasmalogens) is slower than in controls. Quantitative radioautographic study at the ultrastructural level corroborate that the initial increase of the label in Trembler nerve fibers was different in axons, Schwann cells and myelin sheaths. EM radioautographs reveal indeed that the high label content observed in Trembler axons takes place preferentially in the myelinated portions of axons and drops within 1 week. In both myelinated and unmyelinated segments of the axons, the majority of the radioactivity was contained in axolemma and smooth axoplasmic reticulum. The 10-fold increase of label found in the myelin sheath of Trembler nerve fibers at 1 day raises the question of the origin of the labeled EGP, either by a stimulated synthesis in Schwann cells or by transfer from axonally transported phospholipids. In contrast, the label of axons, Schwann cells and myelin sheaths of control nerve remains stable during the same period.     

Myelin sheath survival after guanethidine-induced axonal degeneration

Membrane-membrane interactions between axons and Schwann cells are required for initial myelin formation in the peripheral nervous system. However, recent studies of double myelination in sympathetic nerve have indicated that myelin sheaths continue to exist after complete loss of axonal contact (Kidd, G. J., and J. W. Heath. 1988. J. Neurocytol. 17:245-261). This suggests that myelin maintenance may be regulated either by diffusible axonal factors or by nonaxonal mechanisms. To test these hypotheses, axons involved in double myelination in the rat superior cervical ganglion were destroyed by chronic guanethidine treatment. Guanethidine-induced sympathectomy resulted in a Wallerian-like pattern of myelin degeneration within 10 d. In doubly myelinated configurations the axon, inner myelin sheath (which lies in contact with the axon), and approximately 75% of outer myelin sheaths broke down by this time. Degenerating outer sheaths were not found at later periods. It is probably that outer sheaths that degenerated were only partially displaced from the axon at the commencement of guanethidine treatment. In contrast, analysis of serial sections showed that completely displaced outer internodes remained ultrastructurally intact. These internodes survived degeneration of the axon and inner sheath, and during the later time points (2-6 wk) they enclosed only connective tissue elements and reorganized Schwann cells/processes. Axonal regeneration was not observed within surviving outer internodes. We therefore conclude that myelin maintenance in the superior cervical ganglion is not dependent on direct axonal contact or diffusible axonal factors. In addition, physical association of Schwann cells with the degenerating axon may be an important factor in precipitating myelin breakdown during Wallerian degeneration.     

Role of macrophages in peripheral nerve degeneration and repair.

A cut or crush injury to a peripheral nerve results in the degeneration of that portion of the axon isolated from the cell body. The rapid degeneration of this distal segment was for many years believed to be a process intrinsic to the nerve. It was believed that Schwann cells both phagocytosed degenerating axons and myelin sheaths and also provided growth factors to promote regeneration of the damaged axons. In recent years, it has become apparent that the degenerating distal segment is invaded by monocytes from the blood. We will review the evidence that these recruited macrophages play a role in both degeneration and regeneration of peripheral nerve axons after injury and consider whether the slow degeneration and poor monocyte recruitment in the central nervous system may contribute to the poor regeneration there.     

Immunocytochemical localization of P0 protein in Golgi complex membranes and myelin of developing rat Schwann cells

P0 protein, the dominant protein in peripheral nervous system myelin, was studied immunocytochemically in both developing and mature Schwann cells. Trigeminal and sciatic nerves from newborn, 7-d, and adult rats were processed for transmission electron microscopy. Alternating 1- micrometer-thick Epon sections were stained with paraphenylenediamine (PD) or with P0 antiserum according to the peroxidase-antiperoxidase method. To localize P0 in Schwann cell cytoplasm and myelin membranes, the distribution of immunostaining observed in 1-micrometer sections was mapped on electron micrographs of identical areas found in adjacent thin sections. The first P0 staining was observed around axons and/or in cytoplasm of Schwann cells that had established a 1:1 relationship with axons. In newborn nerves, staining of newly formed myelin sheaths was detected more readily with P0 antiserum than with PD. Myelin sheaths with as few as three lamellae could be identified with the light microscope. Very thin sheaths often stained less intensely and part of their circumference frequently was unstained. Schmidt-Lanterman clefts found in more mature sheaths also were unstained. As myelination progressed, intensely stained myelin rings became much more numerous and, in adult nerves, all sheaths were intensely and uniformly stained. Particulate P0 staining also was observed in juxtanuclear areas of Schwann cell cytoplasm. It was most prominent during development, then decreased, but still was detected in adult nerves. The cytoplasmic areas stained by P0 antiserum were rich in Golgi complex membranes.     

FURTHER OBSERVATIONS ON THE STRUCTURE OF MYELIN SHEATHS IN THE CENTRAL NERVOUS SYSTEM

Direct evidence has been presented to confirm the existence of a spiral in the myelin sheaths of the central nervous system. An account of some of the variations in structure of central myelin sheaths has been given and it has been shown that the radial component of myelin sheaths has the form of a series of rod-like thickenings of the intraperiod line. These thickenings extend along the intraperiod line in a direction parallel to the length of the axon. The relative position of the internal mesaxon and external tongue of cytoplasm has been determined in a number of transverse sections of sheaths from the optic nerves of adult mice, adult rats, and young rats. In about 75 per cent of the mature sheaths examined, these two structures were found within the same quadrant of the sheath, so that the cytoplasm of the external tongue process tends to lie directly outside that associated with the internal mesaxon. The frequency with which the internal mesaxon and external tongue lie within the same quadrant of the sheath increases both with the age of the animal and with the number of lamellae present within a sheath. The possible significance of these findings is discussed.     

Ballooning of myelin sheaths in normally aged macaques

In aged animal brains, a variety of holes are formed in the neuropil. One type of hole, here designated as the myelin balloon, is an abnormality of the myelin sheath and is found in a number of diverse sites in the brain. Profiles of myelin balloons display rather smoothly rounded peripheral contours and typically range up to 10 μm in diameter, although exceptionally large examples may be twice this size. The balloons are bounded by lamellae of myelin, and to accommodate the contents of the balloon, the myelin sheath becomes split at the intraperiod line. Since the intraperiod line is formed by the apposition of the outer faces of the myelin-forming plasma membrane, the contents of the myelin balloons are, in effect, in continuity with the extracellular space, and it is suggested that the contents of the balloons are fluid, with the fluid exerting an outward pressure on the walls of the balloons to produce their spherical shapes. Myelin balloons are not only produced during aging but also occur in a number of genetic strains of mice and in a number of human disease states. They thus represent a non-specific, though distinctive and common, alteration of the myelin sheath and are a reflection of the fact that under a variety of conditions, including normal aging, oligodendrocytes are unable to maintain the integrity of their sheaths.     

N-WASp is required for Schwann cell cytoskeletal dynamics, normal myelin gene expression and peripheral nerve myelination

Schwann cells elaborate myelin sheaths around axons by spirally wrapping and compacting their plasma membranes. Although actin remodeling plays a crucial role in this process, the effectors that modulate the Schwann cell cytoskeleton are poorly defined. Here, we show that the actin cytoskeletal regulator, neural Wiskott-Aldrich syndrome protein (N-WASp), is upregulated in myelinating Schwann cells coincident with myelin elaboration. When N-WASp is conditionally deleted in Schwann cells at the onset of myelination, the cells continue to ensheath axons but fail to extend processes circumferentially to elaborate myelin. Myelin-related gene expression is also severely reduced in the N-WASp-deficient cells and in vitro process and lamellipodia formation are disrupted. Although affected mice demonstrate obvious motor deficits these do not appear to progress, the mutant animals achieving normal body weights and living to advanced age. Our observations demonstrate that N-WASp plays an essential role in Schwann cell maturation and myelin formation.     

THE FINE STRUCTURE OF NERVE CELL BODIES AND THEIR MYELIN SHEATHS IN THE EIGHTH NERVE GANGLION OF THE GOLDFISH

The eighth cranial nerve ganglion consists of bipolar nerve cell bodies each occupying part of an internodal segment. The perikaryal sheaths range from a single layer of Schwann cell cytoplasm on the smallest cells to typical thick compact myelin on the largest. On most perikarya, the sheath displays an intermediate form, consisting of multiple layers of Schwann cell cytoplasm (loose myelin), or of loose and compact myelin continuous with each other. Internodes beyond the one containing the cell body bear only compact myelin. In loose myelin the thickness of each layer of Schwann cell cytoplasm is about 100 A. It may be much greater (~ 3000 A) particularly in the outermost layers of the sheath, or the cytoplasm may thin and even disappear with formation of a major dense line. The cytoplasmic layers are separated from each other by a light zone, 40 to 200 A wide, which in its broader portions may contain an intermediate line. Desmosomes sometimes occur between lamellae. In addition to the usual organelles, the perikaryal cytoplasm contains granular and membranous inclusions. Large cells covered by compact myelin have a consistently higher concentration of neurofilaments, and some of the largest cells, in addition, show a reduced concentration of ribosomes. The functional significance and possible origins of perikaryal myelin sheaths are discussed.     

The need for speed. II. Myelin in calanoid copepods

Speed of nerve impulse conduction is greatly increased by myelin, a multi-layered membranous sheath surrounding axons. Myelinated axons are ubiquitous among the vertebrates, but relatively rare among invertebrates. Electron microscopy of calanoid copepods using rapid cryofixation techniques revealed the widespread presence of myelinated axons. Myelin sheaths of up to 60 layers were found around both sensory and motor axons of the first antenna and interneurons of the ventral nerve cord. Except at nodes, individual lamellae appeared to be continuous and circular, without seams, as opposed to the spiral structure of vertebrate and annelid myelin. The highly organized myelin was characterized by the complete exclusion of cytoplasm from the intracellular spaces of the cell generating it. In regions of compaction, extracytoplasmic space was also eliminated. Focal or fenestration nodes, rather than circumferential ones, were locally common. Myelin lamellae terminated in stepwise fashion at these nodes, appearing to fuse with the axolemma or adjacent myelin lamellae. As with vertebrate myelin, copepod sheaths are designed to minimize both resistive and capacitive current flow through the internodal membrane, greatly speeding nerve impulse conduction. Copepod myelin differs from that of any other group described, while sharing features of every group. Accepted: 8 January 2000     

N-WASP is required for membrane wrapping and myelination by Schwann cells

During peripheral nerve myelination, Schwann cells sort larger axons, ensheath them, and eventually wrap their membrane to form the myelin sheath. These processes involve extensive changes in cell shape, but the exact mechanisms involved are still unknown. Neural Wiskott-Aldrich syndrome protein (N-WASP) integrates various extracellular signals to control actin dynamics and cytoskeletal reorganization through activation of the Arp2/3 complex. By generating mice lacking N-WASP in myelinating Schwann cells, we show that N-WASP is crucial for myelination. In N-WASP-deficient nerves, Schwann cells sort and ensheath axons, but most of them fail to myelinate and arrest at the promyelinating stage. Yet, a limited number of Schwann cells form unusually short internodes, containing thin myelin sheaths, with the occasional appearance of myelin misfoldings. These data suggest that regulation of actin filament nucleation in Schwann cells by N-WASP is crucial for membrane wrapping, longitudinal extension, and myelination.     

Expressing antisense P0 RNA in Schwann cells perturbs myelination.

Primary Schwann cells were infected in vitro with a recombinant retrovirus expressing a dominant selectable marker, neomycin phosphotransferase (conferring resistance to the drug G418), and antisense P0 RNA under the control of the human beta-actin promoter. A proportion of the G418-resistant cells failed to form myelin when cocultured with dorsal root ganglion neurons under conditions that promote Schwann cell differentiation. These cells expressed high levels of P0 antisense RNA. Among the impaired cells, the majority had segregated and ensheathed individual axon but had not differentiated further. They did not express P0 but did express myelin- associated glycoprotein and galactocerebroside. A minority of partially inhibited Schwann cells were also observed that elaborated thin myelin sheaths containing variable numbers of compacted and noncompacted lamellae. These data indicate that restricting the level of P0 expression inhibits spiralling of the Schwann cell membrane and subsequent compaction.     

Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and myelin-associated glycoprotein) in regenerating adult mouse sciatic nerve

The localization of the neural cell adhesion molecules L1, N-CAM, and the myelin-associated glycoprotein was studied by pre- and postembedding staining procedures at the light and electron microscopic levels in transected and crushed adult mouse sciatic nerve. During the first 2-6 d after transection, myelinated and nonmyelinated axons degenerated in the distal part of the proximal stump close to the transection site and over the entire length of the distal part of the transected nerve. During this time, regrowing axons were seen only in the proximal, but not in the distal nerve stump. In most cases L1 and N-CAM remained detectable at cell contacts between nonmyelinating Schwann cells and degenerating axons as long as these were still morphologically intact. Similarly, myelin-associated glycoprotein remained detectable in the periaxonal area of the degenerating myelinated axons. During and after degeneration of axons, nonmyelinating Schwann cells formed slender processes which were L1 and N-CAM positive. They resembled small-diameter axons but could be unequivocally identified as Schwann cells by chronical denervation. Unlike the nonmyelinating Schwann cells, only few myelinating ones expressed L1 and N-CAM. At the cut ends of the nerve stumps a cap developed (more at the proximal than at the distal stump) that contained S-100-negative and fibronectin-positive fibroblast-like cells. Most of these cells were N-CAM positive but always L1 negative. Growth cones and regrowing axons expressed N-CAM and L1 at contact sites with these cells. Regrowing axons of small diameter were L1 and N-CAM positive where they made contact with each other or with Schwann cells, while large-diameter axons were only poorly antigen positive or completely negative. 14 d after transection, when regrowing axons were seen in the distal part of the transected nerve, regrowing axons made L1- and N-CAM-positive contacts with Schwann cells. When contacting basement membrane, axons were rarely found to express L1 and N-CAM. Most, if not all, Schwann cells associated with degenerating myelin expressed L1 and N-CAM. In crushed nerves, the immunostaining pattern was essentially the same as in the cut nerve. During formation of myelin, the sequence of adhesion molecule expression was the same as during development: L1 disappeared and N-CAM was reduced on myelinating Schwann cells and axons after the Schwann cell process had turned approximately 1.5 loops around the axon. Myelin-associated glycoprotein then appeared both periaxonally and on the turning loops of Schwann cells in the uncompacted myelin.(ABSTRACT TRUNCATED AT 400 WORDS)     

Schwann cells in the regenerating fish optic nerve: Evidence that CNS axons,not the glia,determine when myelin formation begins

Fish optic nerve fibres quickly regenerate after injury, but the onset of remyelination is delayed until they reach the brain. This recapitulates the timetable of CNS myelinogenesis during development in vertebrate animals generally, and we have used the regenerating fish optic nerve to obtain evidence that it is the axons, not the myelinating glial cells, that determine when myelin formation begins. In fish, the site of an optic nerve injury becomes remyelinated by ectopic Schwann cells of unknown origin. We allowed these cells to become established and then used them as reporters to indicate the time course of pro-myelin signalling during a further round of axonal outgrowth following a second upstream lesion. Unlike in the mammalian PNS, the ectopic Schwann cells failed to respond to axotomy and to the initial outgrowth of new optic axons. They only began to divide after the axons had reached the brain. Shortly afterwards, small numbers of Schwann cells began to leave the dividing pool and form myelin sheaths. More followed gradually, so that by 3 months remyelination was almost completed and few dividing cells were left. Moreover, remyelination occurred synchronously throughout the optic nerve, with the same time course in the pre-existing Schwann cells, the new ones that colonised the second injury, and the CNS oligodendrocytes elsewhere. The optic axons are the only common structures that could synchronise myelin formation in these disparate glial populations. The responses of the ectopic Schwann cells suggest that they are controlled by the regenerating optic axons in two consecutive steps. First, they begin to proliferate when the growing axons reach the brain. Second, they leave the cell cycle to differentiate individually at widely different times during the ensuing 2 months, during the critical period when the initial rough pattern of axon terminals in the optic tectum becomes refined into an accurate map. We suggest that each axon signals individually for myelin ensheathment once it completes this process.     

THE GEOMETRY OF PERIPHERAL MYELIN SHEATHS DURING THEIR FORMATION AND GROWTH IN RAT SCIATIC NERVES

In rat sciatic nerves, a small bundle of fibers was identified in which myelin sheaths were absent at birth, appeared within 3 days, and grew rapidly for 2 wk. During this interval, nerves were removed from littermates and were sectioned serially in the transverse plane. Alternating sets of thin and thick sections were used to prepare electron micrograph montages in which single myelinating axons could be identified and traced distally. During the formation of the first spiral turn, the mesaxon's length and configuration varied when it was studied at different levels in the same Schwann cell. The position of the mesaxon's termination shifted while its origin, at the Schwann cell surface, remained relatively constant. Along myelin internodes composed of two to six spiral turns, there were many variations in the number of lamellae and their contour. Near the mesaxon's origin, longitudinal strips of cytoplasm separated the myelin layers. Thicker sheaths were larger in circumference, more circular in transverse sections, and more uniform at different levels. Irregularities were confined to the paranodal region, and separation of lamellae by cytoplasm occurred at Schmidt-Lantermann clefts. Approximate dimensions of the bundle, its largest fibers, and their myelin sheaths were measured and calculated. The myelin membrane's transverse length and area increased exponentially with time; the growth rate increased rapidly during the formation of the first four to six spiral layers and remained relatively constant during the subsequent enlargement of the compact sheath.     

Direct visualization of membrane architecture of myelinating cells in transgenic mice expressing membrane‐anchored EGFP

Myelinogenesis is a complex process that involves substantial and dynamic changes in plasma membrane architecture and myelin interaction with axons. Highly ramified processes of oligodendrocytes in the central nervous system (CNS) make axonal contact and then extrapolate to wrap around axons and form multilayer compact myelin sheathes. Currently, the mechanisms governing myelin sheath assembly and axon selection by myelinating cells are not fully understood. Here, we generated a transgenic mouse line expressing the membrane‐anchored green fluorescent protein (mEGFP) in myelinating cells, which allow live imaging of details of myelinogenesis and cellular behaviors in the nervous systems. mEGFP expression is driven by the promoter of 2'‐3'‐cyclic nucleotide 3'‐phosphodiesterase (CNP) that is expressed in the myelinating cell lineage. Robust mEGFP signals appear in the membrane processes of oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system (PNS), wherein mEGFP expression defines the inner layers of myelin sheaths and Schmidt‐Lanterman incisures in adult sciatic nerves. In addition, mEGFP expression can be used to track the extent of remyelination after demyelinating injury in a toxin‐induced demyelination animal model. Taken together, the membrane‐anchored mEGFP expression in the new transgenic line would facilitate direct visualization of dynamic myelin membrane formation and assembly during development and process remodeling during remyelination after various demyelinating injuries. genesis 52:341–349, 2014. © 2014 Wiley Periodicals, Inc.