The Experts below are selected from a list of 255 Experts worldwide ranked by ideXlab platform
David A Lyons - One of the best experts on this subject based on the ideXlab platform.
-
Ca^2+ activity signatures of Myelin Sheath formation and growth in vivo
Nature Neuroscience, 2018Co-Authors: Marion Baraban, Sigrid Koudelka, David A LyonsAbstract:The authors live-image zebrafish Myelin Sheath Ca^2+ activity in vivo and find that high-amplitude long-duration Ca^2+ transients precede calpain-dependent Sheath retractions while frequent low-amplitude short-duration transients drive Sheath growth. During Myelination, individual oligodendrocytes initially over-produce short Myelin Sheaths, which are either retracted or stabilized. By live-imaging oligodendrocyte Ca^2+ activity in vivo, we find that high-amplitude, long-duration Ca^2+ transients in Sheaths prefigure retractions, mediated by calpain. Following stabilization, Myelin Sheaths grow along axons, and we find that higher-frequency Ca^2+ transient activity in Sheaths precedes faster elongation. Our data implicate local Ca^2+ signaling in regulating distinct stages of Myelination.
-
synaptic vesicle release regulates Myelin Sheath number of individual oligodendrocytes in vivo
Nature Neuroscience, 2015Co-Authors: Sigrid Mensch, Marion Baraban, Rafael G Almeida, Tim Czopka, Jessica Ausborn, Abdeljabbar El Manira, David A LyonsAbstract:The Myelination of axons by oligodendrocytes markedly affects CNS function, but how this is regulated by neuronal activity in vivo is not known. We found that blocking synaptic vesicle release impaired CNS Myelination by reducing the number of Myelin Sheaths made by individual oligodendrocytes during their short period of formation. We also found that stimulating neuronal activity increased Myelin Sheath formation by individual oligodendrocytes. These data indicate that neuronal activity regulates the Myelinating capacity of single oligodendrocytes.
-
axonal selection and Myelin Sheath generation in the central nervous system
Current Opinion in Cell Biology, 2013Co-Authors: Mikael Simons, David A LyonsAbstract:The formation of Myelin in the central nervous system is a multi-step process that involves coordinated cell-cell interactions and dramatic changes in plasma membrane architecture. First, oligodendrocytes send our numerous highly ramified processes to sample the axonal environment and decide which axon(s) to select for Myelination. After this decision is made and individual axon to oligodendrocyte contact has been established, the exploratory process of the oligodendrocyte is converted into a flat Sheath that spreads and winds along and around its associated axon to generate a multilayered membrane stack. By compaction of the opposing extracellular layers of membrane and extrusion of almost all cytoplasm from the intracellular domain of the Sheath, the characteristic membrane-rich multi-lamellar structure of Myelin is formed. Here we highlight recent advances in identifying biophysical and signalling based mechanisms that are involved in axonal selection and Myelin Sheath generation by oligodendrocytes. A thorough understanding of the mechanisms underlying these events is a prerequisite for the design of novel Myelin repair strategies in deMyelinating and dysMyelinating diseases.
Yousheng Shu - One of the best experts on this subject based on the ideXlab platform.
-
Cell vibron polariton resonantly self-confined in the Myelin Sheath of nerve
Nano Research, 2019Co-Authors: Bo Song, Yousheng ShuAbstract:Polaritons are arousing tremendous interests in physics and material sciences for their unique and amazing properties, especially including the condensation, lasing without inversion and even room-temperature superfluidity. Herein, we propose a cell vibron polariton (cell-VP): a collectively coherent mode of a photon and all phospholipid molecules in a Myelin Sheath formed by glial cells. Cell-VP can be resonantly self-confined in the Myelin Sheath under physiological conditions. The observations benefit from the specifically compact, ordered and polar thin-film structure of the Sheath, and the relatively strong coupling of the mid-infrared photon with the vibrons of phospholipid tails in the Myelin. The underlying physics is revealed to be the collectively coherent superposition of the photon and vibrons, the polariton induced significant enhancement of Myelin permittivity, and the resonance of the polariton with the Sheath. The captured cell-VPs in Myelin Sheaths may provide a promising way for super-efficient consumption of extra-weak bioenergy and even directly serve for quantum information. These findings further the understanding of nervous system operations at cellular level from the view of quantum mechanics.
-
Cell vibron polariton in the Myelin Sheath of nerve
arXiv: General Physics, 2019Co-Authors: Bo Song, Yousheng ShuAbstract:Polaritons are arousing tremendous interests in physics and material sciences for their unique and amazing properties, especially including the condensation, lasing without inversion and even room-temperature superfluidity. Herein, we propose a cell vibron polariton (cell-VP): a collectively coherent mode of a photon and all phospholipid molecules in a Myelin Sheath which is a nervous cell majorly consisting of the phospholipid molecules. Cell-VP can be resonantly self-confined in the Myelin Sheath under physiological conditions. The observations benefit from the specifically compact, ordered and polar thin-film structure of the Sheath, and the relatively strong coupling of the mid-infrared photon with the vibrons of phospholipid tails in the Myelin. The underlying physics is revealed to be the collectively coherent superposition of the photon and vibrons, the polariton induced significant enhancement of Myelin permittivity, and the resonance of the polariton with the Sheath cell. The captured cell-VPs in Myelin Sheaths may provide a promising way for super-efficient consumption of extra-weak bioenergy and even directly serve for quantum information in the nervous system. These findings further the understanding of neuroscience on the cellular level from the view of quantum mechanics.
Bruce Appel - One of the best experts on this subject based on the ideXlab platform.
-
The Akt-mTOR pathway drives Myelin Sheath growth by regulating cap-dependent translation
2021Co-Authors: Karlie N. Fedder-semmes, Bruce AppelAbstract:ABSTRACTIn the vertebrate central nervous system, oligodendrocytes produce Myelin, a specialized proteolipid rich membrane, to insulate and support axons. Individual oligodendrocytes wrap multiple axons with Myelin Sheaths of variable lengths and thicknesses. Myelin grows at the distal ends of oligodendrocyte processes and multiple lines of work have provided evidence that mRNAs and RNA binding proteins localize to Myelin, together supporting a model where local translation controls Myelin Sheath growth. What signal transduction mechanisms could control this? One strong candidate is the Akt-mTOR pathway, a major cellular signaling hub that coordinates transcription, translation, metabolism, and cytoskeletal organization. Here, using zebrafish as a model system, we found that Akt-mTOR signaling promotes Myelin Sheath growth and stability during development. Through cell-specific manipulations to oligodendrocytes, we show that the Akt-mTOR pathway drives cap-dependent translation to promote Myelination and that restoration of cap-dependent translation is sufficient to rescue Myelin deficits in mTOR loss-of-function animals. Moreover, an mTOR-dependent translational regulator co-localized with mRNA encoding a canonically Myelin-translated protein in vivo and bioinformatic investigation revealed numerous putative translational targets in the Myelin transcriptome. Together, these data raise the possibility that Akt-mTOR signaling in nascent Myelin Sheaths promotes Sheath growth via translation of Myelin-resident mRNAs during development.SIGNIFICANCE STATEMENTIn the brain and spinal cord oligodendrocytes extend processes that tightly wrap axons with Myelin, a protein and lipid rich membrane that increases electrical impulses and provides trophic support. Myelin membrane grows dramatically following initial axon wrapping in a process that demands protein and lipid synthesis. How protein and lipid synthesis is coordinated with the need for Myelin to be generated in certain locations remains unknown. Our study reveals that the Akt-mTOR signaling pathway promotes Myelin Sheath growth by regulating protein translation. Because we found translational regulators of the Akt-mTOR pathway in Myelin, our data raise the possibility Akt-mTOR activity regulates translation in Myelin Sheaths to deliver Myelin on demand to the places it is needed.
-
The RNA binding protein fragile X mental retardation protein promotes Myelin Sheath growth.
Glia, 2019Co-Authors: Caleb A. Doll, Katie M. Yergert, Bruce AppelAbstract:During development, oligodendrocytes in the central nervous system extend a multitude of processes that wrap axons with Myelin. The highly polarized oligodendrocytes generate Myelin Sheaths on many different axons, which are far removed from the cell body. Neurons use RNA binding proteins to transport, stabilize, and locally translate mRNA in distal domains of neurons. Local synthesis of synaptic proteins during neurodevelopment facilitates the rapid structural and functional changes underlying neural plasticity and avoids extensive protein transport. We hypothesize that RNA binding proteins also regulate local mRNA regulation in oligodendrocytes to promote Myelin Sheath growth. Fragile X mental retardation protein (FMRP), an RNA binding protein that plays essential roles in the growth and maturation of neurons, is also expressed in oligodendrocytes. To determine whether oligodendrocytes require FMRP for Myelin Sheath development, we examined fmr1-/- mutant zebrafish and drove FMR1 expression specifically in oligodendrocytes. We found oligodendrocytes in fmr1-/- mutants developed Myelin Sheaths of diminished length, a phenotype that can be autonomously rescued in oligodendrocytes with FMR1 expression. Myelin basic protein (Mbp), an essential Myelin protein, was reduced in Myelin tracts of fmr1-/- mutants, but loss of FMRP function did not impact the localization of mbpa transcript in Myelin. Finally, expression of FMR1-I304N, a missense allele that abrogates FMRP association with ribosomes, failed to rescue fmr1-/- mutant Sheath growth and induced short Myelin Sheaths in oligodendrocytes of wild-type larvae. Taken together, these data suggest that FMRP promotes Sheath growth through local regulation of translation.
-
oligodendrocytes express synaptic proteins that modulate Myelin Sheath formation
Nature Communications, 2019Co-Authors: Alexandria N Hughes, Bruce AppelAbstract:Vesicular release from neurons promotes Myelin Sheath growth on axons. Oligodendrocytes express proteins that allow dendrites to respond to vesicular release at synapses, suggesting that axon-Myelin contacts use similar communication mechanisms as synapses to form Myelin Sheaths. To test this, we used fusion proteins to track synaptic vesicle localization and membrane fusion in zebrafish during developmental Myelination and investigated expression and localization of PSD95, a dendritic post-synaptic protein, within oligodendrocytes. Synaptic vesicles accumulate and exocytose at enSheathment sites with variable patterning and most Sheaths localize PSD95 with patterning similar to exocytosis site location. Disruption of candidate PDZ-binding transsynaptic adhesion proteins in oligodendrocytes cause variable effects on Sheath length and number. One candidate, Cadm1b, localizes to Myelin Sheaths where both PDZ binding and extracellular adhesion to axons mediate Sheath growth. Our work raises the possibility that axon-glial communication contributes to Myelin plasticity, providing new targets for mechanistic unraveling of developmental Myelination.
-
The RNA Binding Protein FMRP Promotes Myelin Sheath Growth
2019Co-Authors: Caleb A. Doll, Katie M. Yergert, Bruce AppelAbstract:During development, oligodendrocytes in the central nervous system extend a multitude of processes that wrap axons with Myelin. The highly polarized oligodendrocytes generate Myelin Sheaths on many different axons, which are far removed from the cell body. Neurons use RNA binding proteins to transport, stabilize, and locally translate mRNA in distal domains of neurons. Local synthesis of synaptic proteins during neurodevelopment facilitates the rapid structural and functional changes underlying neural plasticity and avoids extensive protein transport. We hypothesize that RNA binding proteins also regulate local mRNA regulation in oligodendrocytes to promote Myelin Sheath growth. Fragile X mental retardation protein (FMRP), an RNA binding protein that plays essential roles in the growth and maturation of neurons, is also expressed in oligodendrocytes. To determine whether oligodendrocytes require FMRP for Myelin Sheath development, we examined fmr1-/- mutant zebrafish and drove FMR1 expression specifically in oligodendrocytes. We found oligodendrocytes in fmr1-/- mutants developed Myelin Sheaths of diminished length, a phenotype that can be autonomously rescued in oligodendrocytes with FMR1 expression. Myelin basic protein (Mbp), an essential Myelin protein, was reduced in Myelin tracts of fmr1-/- mutants, but loss of FMRP function did not impact the localization of mbpa transcript in Myelin. Finally, expression of FMR1-I304N, a missense allele that abrogates FMRP association with ribosomes, failed to rescue fmr1-/- mutant Sheath growth and induced short Myelin Sheaths in oligodendrocytes of wild-type larvae. Taken together, these data suggest that FMRP promotes Sheath growth through local regulation of translation.
Nicolas Tricaud - One of the best experts on this subject based on the ideXlab platform.
-
Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation
Frontiers Media S.A., 2018Co-Authors: Nicolas TricaudAbstract:Myelin Sheath geometry, encompassing Myelin Sheath thickness relative to internodal length, is critical to optimize nerve conduction velocity and these parameters are carefully adjusted by the Myelinating cells in mammals. In the central nervous system these adjustments could regulate neuronal activities while in the peripheral nervous system they lead to the optimization and the reliability of the nerve conduction velocity. However, the physiological and cellular mechanisms that underlie Myelin Sheath geometry regulation are not yet fully elucidated. In peripheral nerves the Myelinating Schwann cell uses several molecular mechanisms to reach and maintain the correct Myelin Sheath geometry, such that Myelin Sheath thickness and internodal length are regulated independently. One of these mechanisms is the epithelial-like cell polarization process that occurs during the early phases of the Myelin biogenesis. Epithelial cell polarization factors are known to control cell size and morphology in invertebrates and mammals making these processes critical in the organogenesis. Correlative data indicate that internodal length is regulated by postnatal body growth that elongates peripheral nerves in mammals. In addition, the mechanical stretching of peripheral nerves in adult animals shows that Myelin Sheath length can be increased by mechanical cues. Recent results describe the important role of YAP/TAZ co-transcription factors during Schwann cell Myelination and their functions have linked to the mechanotransduction through the HIPPO pathway and the epithelial polarity factor Crb3. In this review the molecular mechanisms that govern mechanically-driven Myelin Sheath elongation and how a Schwann cell can modulate internodal Myelin Sheath length, independent of internodal thickness, will be discussed regarding these recent data. In addition, the potential relevance of these mechanosensitive mechanisms in peripheral pathologies will be highlighted
-
In vivo time-lapse imaging of mitochondria in healthy and diseased peripheral Myelin Sheath
Mitochondrion, 2015Co-Authors: Sergio Gonzalez, Ruani Fernando, Jade Berthelot, Claire Perrin-tricaud, Emmanuelle Sarzi, Roman Chrast, Guy Lenaers, Nicolas TricaudAbstract:The Myelin Sheath that covers a large amount of neurons is critical for their homeostasis, and Myelinating glia mitochondria have recently been shown to be essential for neuron survival. However morphological and physiological properties of these organelles remain elusive. Here we report a method to analyze mitochondrial dynamics and morphology in Myelinating Schwann cells of living mice using viral transduction and time-lapse multiphoton microscopy. We describe the distribution, shape, size and dynamics of mitochondria in live cells. We also report mitochondrial alterations in Opa1(delTTAG) mutant mice cells at presymptomatic stages, suggesting that mitochondrial defects in Myelin contribute to OPA1 related neuropathy and represent a biomarker for the disease.
-
Pals1 Is a Major Regulator of the Epithelial-Like Polarization and the Extension of the Myelin Sheath in Peripheral Nerves
The Journal of Neuroscience, 2010Co-Authors: Murat Özçelik, Laurent Cotter, Claire Jacob, Joao B Relvas, Ueli Suter, Jorge A. Pereira, Nicolas TricaudAbstract:Diameter, organization, and length of the Myelin Sheath are important determinants of the nerve conduction velocity, but the basic molecular mechanisms that control these parameters are only partially understood. Cell polarization is an essential feature of differentiated cells, and relies on a set of evolutionarily conserved cell polarity proteins. We investigated the molecular nature of Myelin Sheath polarization in connection with the functional role of the cell polarity protein pals1 (Protein Associated with Lin Seven 1) during peripheral nerve Myelin Sheath extension. We found that, in regard to epithelial polarity, the Schwann cell outer abaxonal domain represents a basolateral-like domain, while the inner adaxonal domain and Schmidt–Lanterman incisures form an apical-like domain. Silencing of pals1 in Myelinating Schwann cells in vivo resulted in a severe reduction of Myelin Sheath thickness and length. Except for some infoldings, the structure of compact Myelin was not fundamentally affected, but cells produced less Myelin turns. In addition, pals1 is required for the normal polarized localization of the vesicular markers sec8 and syntaxin4, and for the distribution of E-cadherin and Myelin proteins PMP22 and MAG at the plasma membrane. Our data show that the polarity protein pals1 plays an essential role in the radial and longitudinal extension of the Myelin Sheath, likely involving a functional role in membrane protein trafficking. We conclude that regulation of epithelial-like polarization is a critical determinant of Myelin Sheath structure and function.
Robert A. Lazzarini - One of the best experts on this subject based on the ideXlab platform.
-
Schwann cells and oligodendrocytes read distinct signals in establishing Myelin Sheath thickness
Journal of neuroscience research, 2001Co-Authors: Gregory A. Elder, Victor L. Friedrich, Robert A. LazzariniAbstract:Schwann cells and oligodendrocytes produce Myelin Sheaths of widely varying sizes. How these cells determine the size of Myelin Sheath for a particular axon is incompletely understood. Axonal diameter has long been suspected to be a signal in this process. We have analyzed Myelin Sheath thickness in L5 lumbar root and spinal cord white matter of a series of mouse mutants with diminished axonal calibers resulting from a deficiency of neurofilaments (NFs). In the PNS, average axonal diameters were reduced by 20 ‐37% in the NF mutants. Remarkably, the average Myelin Sheath thickness remained unchanged from control values, and regression analysis showed Sheaths abnormally thick for a given size of axon. These data show that a genetically induced reduction in axonal caliber does not cause a reduction in Myelin Sheath thickness in PNS and indicate that Schwann cells read some intrinsic signal on axons that can be uncoupled from axonal diameter. Interestingly, Myelin Sheaths in the spinal cord of these animals were not abnormally thick, arguing that axonal diameter may contribute directly to the regulation of Myelination in the CNS and that oligodendrocytes and Schwann cells use different cues to set Myelin Sheath thickness. J. Neurosci. Res. 65:493‐ 499, 2001. © 2001 Wiley-Liss, Inc.
