Oligodendrocytes regulate formation of nodes of Ranvier via the recognition molecule OMgp

Nie, Duyu; Law, Janice W. S.; Chia, Chern Pang; Dhingra, Narender K.; Shimoda, Yasushi; Yang, Wu Lin; Gong, Ningqiang; Chen, Qing Wen; Xu, Gang; Hu, Qi Dong; Chow, Pierce K. H.; Ng, Yen Kaow; Ling, Eng Ang; Watanabe, Kazutada; Xu, Tian; Habib, Amyn A.; Schachner, Melitta; Xiao, Zhi‐Cheng

doi:10.1017/s1740925x06000251

Cited by 27 publications

(39 citation statements)

References 49 publications

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“…Notably, netrin-1 labeling was selectively enriched in perinodal regions, based on localization with the perinodal marker Caspr. Perinodal localization has been observed previously also with the myelinassociated inhibitors OMgp and MAG (Huang et al, 2005;Nie et al, 2006). Netrin-1 expression persisted 3 months after spinal cord injury (Fig.…”

Section: Netrin-1 Is Expressed By Mature Oligodendrocytes In the Adulsupporting

confidence: 76%

“…Both netrin-1 and its receptors are expressed in the intact and lesioned adult CNS. Netrin-1 is expressed by oligodendrocytes, and is enriched in proximity to paranodal loops at nodes of Ranvier in adult white matter, in a location similar to that described for two other myelin-associated inhibitors, OMgp and MAG (Huang et al, 2005;Nie et al, 2006). The repulsion-mediating class of netrin UNC5 receptors is expressed by rubrospinal and corticospinal motor neurons, and by neurons in all laminas of spinal cord gray matter.…”

Section: Discussionmentioning

confidence: 61%

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Netrin-1 Is a Novel Myelin-Associated Inhibitor to Axon Growth

et al. 2008

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We investigated the influence of the bifunctional guidance molecule netrin-1 on axonal growth in the injured adult spinal cord. In the adult, netrin-1 is expressed on mature oligodendrocytes, cells of the central canal, and the meninges. Netrin-1 protein in white matter is selectively enriched adjacent to paranodal loops of myelin in nodes of Ranvier. The repulsion-mediating netrin-1 uncoordinated-5 (UNC5) receptors are expressed by neurons of the corticospinal and rubrospinal projections, and by intrinsic neurons of the spinal cord, both before and after spinal cord injury. Neutralization of netrin-1 in myelin prepared from adult rat spinal cord using UNC5 receptor bodies increases neurite outgrowth from UNC5-expressing spinal motor neurons in vitro. Furthermore, axon regeneration is inhibited in a netrin-1-enriched zone, devoid of other myelin-associated inhibitors, within spinal cord lesion sites in vivo. We conclude that netrin-1 is a novel oligodendrocyte-associated inhibitor that can contribute to axonal growth failure after adult spinal cord injury.

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Section: Netrin-1 Is Expressed By Mature Oligodendrocytes In the Adulsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 61%

Netrin-1 Is a Novel Myelin-Associated Inhibitor to Axon Growth

et al. 2008

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“…However, recent studies have reported NogoA involvement in cell migration and axonal fasciculation during brain development (Mingorance et al, 2004;Mingorance-Le Meur et al, 2007). The same happens with other MAIs such us Omgp with key roles in the formation of nodes of Ranvier (Nie et al, 2006).…”

Section: Introductionmentioning

confidence: 79%

“…This could either indicate a redundant role that can be compensated upon Lingo-1 or NgR1 loss by other gene products or its implication in cell processes not analyzed to date. For example, the participation of Nogo-A or Omgp in functions different from those associated to axonal regeneration has been recently revealed (Nie et al, 2006;Voeltz et al, 2006;Mingorance-Le Meur et al, 2007). As indicated, further studies will be required to ascertain these possibilities.…”

Section: Lingo-1 Protein Is Present In Neurons and In Immature Oligodmentioning

confidence: 99%

Developmental analysis of Lingo‐1/Lern1 protein expression in the mouse brain: Interaction of its intracellular domain with Myt1l

Llorens

Gil

Iraola

et al. 2008

Developmental Neurobiology

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Lingo-1 (also known as Lern1) is a component of the Nogo receptor complex that mediates intracellular signaling in response to myelin associated inhibitors (MAIs): NogoA, MAG, and Omgp. Signaling through Nogo receptor extends to more than its well known role in preventing axon regeneration after lesion in the CNS, being implicated in neuronal functional maturation. Using Lingo-1-deficient mice, it has been demonstrated that Lingo-1 plays relevant roles in oligodendrocyte differentiation during brain development, and that treatment with Lingo-1 antagonists can improve axon regeneration after lesion in adult mice by decreasing MAI mediated signaling. However, a detailed description of the pattern of expression of Lingo-1 protein in correlation with the other partners of Nogo receptor is missing. Here, we show that components of the Nogo receptor complex, Lingo-1, NgR1, p75, and TROY coexist in mouse brain in a defined time window only at later postnatal stages. We have also determined the Lingo-1 distribution showing expression in particular subsets of neurons, but not in myelinating mature oligodendrocytes. Surprisingly, Lingo-1 is expressed at early developmental stages without NgR1, which supports the notion that Lingo-1 may participate in other activities in developing neurons different from oligodendrocyte maturation or axon extension inhibition in the adult. Finally, we propose that the intracellular domain of Lingo-1 contributes to signaling and show that it interacts with the postmitotic neuronal specific zinc finger protein Myt1l, suggesting that Lingo-1 may regulate Myt1l transcription factor activity by affecting its subcellular localization.

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“…52 The ordered arrangement of ion channels at the nodes of Ranvier (and therefore conductive properties of axons) also critically depends on correct myelination. 53 Oligodendrocytes are considered to be essential to long-term axonal integrity, potentially through trophic support mechanisms and axon−glia metabolic coupling mechanisms 54,55 leading to a widely held view that axon− myelin interactions have an important neuroprotective role (and by extension impact disease progression when perturbed). 16 Consequently, CS-induced delays in myelination are of significant clinical importance when considering treatment of a range of pediatric and adult pathologies.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Identifying the Cellular Targets of Drug Action in the Central Nervous System Following Corticosteroid Therapy

Jenkins

Pickard

Khong

et al. 2013

ACS Chem. Neurosci.

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Corticosteroid (CS) therapy is used widely in the treatment of a range of pathologies, but can delay production of myelin, the insulating sheath around central nervous system nerve fibers. The cellular targets of CS action are not fully understood, that is, "direct" action on cells involved in myelin genesis [oligodendrocytes and their progenitors the oligodendrocyte precursor cells (OPCs)] versus "indirect" action on other neural cells. We evaluated the effects of the widely used CS dexamethasone (DEX) on purified OPCs and oligodendrocytes, employing complementary histological and transcriptional analyses. Histological assessments showed no DEX effects on OPC proliferation or oligodendrocyte genesis/maturation (key processes underpinning myelin genesis). Immunostaining and RT-PCR analyses show that both cell types express glucocorticoid receptor (GR; the target for DEX action), ruling out receptor expression as a causal factor in the lack of DEX-responsiveness. GRs function as ligand-activated transcription factors, so we simultaneously analyzed DEX-induced transcriptional responses using microarray analyses; these substantiated the histological findings, with limited gene expression changes in DEX-treated OPCs and oligodendrocytes. With identical treatment, microglial cells showed profound and global changes post-DEX addition; an unexpected finding was the identification of the transcription factor Olig1, a master regulator of myelination, as a DEX responsive gene in microglia. Our data indicate that CS-induced myelination delays are unlikely to be due to direct drug action on OPCs or oligodendrocytes, and may occur secondary to alterations in other neural cells, such as the immune component. To the best of our knowledge, this is the first comparative molecular and cellular analysis of CS effects in glial cells, to investigate the targets of this major class of anti-inflammatory drugs as a basis for myelination deficits.

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Oligodendrocytes regulate formation of nodes of Ranvier via the recognition molecule OMgp

Cited by 27 publications

References 49 publications

Netrin-1 Is a Novel Myelin-Associated Inhibitor to Axon Growth

Netrin-1 Is a Novel Myelin-Associated Inhibitor to Axon Growth

Developmental analysis of Lingo‐1/Lern1 protein expression in the mouse brain: Interaction of its intracellular domain with Myt1l

Identifying the Cellular Targets of Drug Action in the Central Nervous System Following Corticosteroid Therapy

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