The Experts below are selected from a list of 2916 Experts worldwide ranked by ideXlab platform
Evangelia Giannakouri - One of the best experts on this subject based on the ideXlab platform.
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Oligodendrocyte Precursor Cell specification is regulated by bidirectional neural progenitor endothelial Cell crosstalk
Nature Neuroscience, 2021Co-Authors: Isidora Paredes, Jose Ricardo Vieira, Bhavin Shah, Carla F Ramunno, Julia Dyckow, Heike Adler, Melanie Richter, Geza Schermann, Evangelia GiannakouriAbstract:Neural-derived signals are crucial regulators of CNS vascularization. However, whether the vasculature responds to these signals by means of elongating and branching or in addition by building a feedback response to modulate neurodevelopmental processes remains unknown. In this study, we identified bidirectional crosstalk between the neural and the vascular compartment of the developing CNS required for Oligodendrocyte Precursor Cell specification. Mechanistically, we show that neural progenitor Cells (NPCs) express angiopoietin-1 (Ang1) and that this expression is regulated by Sonic hedgehog. We demonstrate that NPC-derived Ang1 signals to its receptor, Tie2, on endothelial Cells to induce the production of transforming growth factor beta 1 (TGFβ1). Endothelial-derived TGFβ1, in turn, acts as an angiocrine molecule and signals back to NPCs to induce their commitment toward Oligodendrocyte Precursor Cells. This work demonstrates a true bidirectional collaboration between NPCs and the vasculature as a critical regulator of oligodendrogenesis. Paredes et al. identify bidirectional crosstalk between the neural and the vascular compartment in the developing CNS required for Oligodendrocyte Precursor Cell specification and mediated by an angiopoietin1–Tie2–TGFs1 signaling axis.
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Oligodendrocyte Precursor Cell specification is regulated by bidirectional neural progenitor endothelial Cell crosstalk
Nature Neuroscience, 2021Co-Authors: Isidora Paredes, Jose Ricardo Vieira, Bhavin Shah, Carla F Ramunno, Julia Dyckow, Heike Adler, Melanie Richter, Geza Schermann, Evangelia GiannakouriAbstract:Neural-derived signals are crucial regulators of CNS vascularization. However, whether the vasculature responds to these signals by means of elongating and branching or in addition by building a feedback response to modulate neurodevelopmental processes remains unknown. In this study, we identified bidirectional crosstalk between the neural and the vascular compartment of the developing CNS required for Oligodendrocyte Precursor Cell specification. Mechanistically, we show that neural progenitor Cells (NPCs) express angiopoietin-1 (Ang1) and that this expression is regulated by Sonic hedgehog. We demonstrate that NPC-derived Ang1 signals to its receptor, Tie2, on endothelial Cells to induce the production of transforming growth factor beta 1 (TGFβ1). Endothelial-derived TGFβ1, in turn, acts as an angiocrine molecule and signals back to NPCs to induce their commitment toward Oligodendrocyte Precursor Cells. This work demonstrates a true bidirectional collaboration between NPCs and the vasculature as a critical regulator of oligodendrogenesis.
Fernando De Castro - One of the best experts on this subject based on the ideXlab platform.
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human adult Oligodendrocyte Precursor Cell biology the bottleneck for effective pro remyelinating therapies for multiple sclerosis
2017Co-Authors: Fernando De CastroAbstract:During pre- and postnatal development, mature Oligodendrocytes derive from Oligodendrocyte Precursor Cells (OPCs).
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Erratum to: Anosmin-1 over-expression regulates Oligodendrocyte Precursor Cell proliferation, migration and myelin sheath thickness
Brain Structure and Function, 2015Co-Authors: Verónica Murcia-belmonte, Pedro F. Esteban, José L. Martínez-hernández, Agnès Gruart, Rafael Luján, José M. Delgado-garcía, Fernando De CastroAbstract:During development of the central nervous system, anosmin-1 (A1) works as a chemotropic cue contributing to axonal outgrowth and collateralization, as well as modulating the migration of different Cell types, fibroblast growth factor receptor 1 (FGFR1) being the main receptor involved in all these events. To further understand the role of A1 during development, we have analysed the over-expression of human A1 in a transgenic mouse line. Compared with control mice during development and in early adulthood, A1 over-expressing transgenic mice showed an enhanced Oligodendrocyte Precursor Cell (OPC) proliferation and a higher number of OPCs in the subventricular zone and in the corpus callosum (CC). The migratory capacity of OPCs from the transgenic mice is increased in vitro due to a higher basal activation of ERK1/2 mediated through FGFR1 and they also produced more myelin basic protein (MBP). In vivo, the over-expression of A1 resulted in an elevated number of mature Oligodendrocytes with higher levels of MBP mRNA and protein, as well as increased levels of activation of the ERK1/2 proteins, while electron microscopy revealed thicker myelin sheaths around the axons of the CC in adulthood. Also in the mature CC, the nodes of Ranvier were significantly longer and the conduction velocity of the nerve impulse in vivo was significantly increased in the CC of A1 over-expressing transgenic mice. Altogether, these data confirmed the involvement of A1 in oligodendrogliogenesis and its relevance for myelination.
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the effect of glia glia interactions on Oligodendrocyte Precursor Cell biology during development and in demyelinating diseases
Frontiers in Cellular Neuroscience, 2013Co-Authors: Diego Clemente, Maria Cristina Ortega, Carolina Melerojerez, Fernando De CastroAbstract:Oligodendrocyte Precursor Cells (OPCs) originate in specific areas of the developing central nervous system (CNS). Once generated, they migrate towards their destinations where they differentiate into mature Oligodendrocytes. In the adult, 5–8% of all Cells in the CNS are OPCs, Cells that retain the capacity to proliferate, migrate, and differentiate into Oligodendrocytes. Indeed, these endogenous OPCs react to damage in demyelinating diseases, like multiple sclerosis (MS), representing a key element in spontaneous remyelination. In the present work, we review the specific interactions between OPCs and other glial Cells (astrocytes, microglia) during CNS development and in the pathological scenario of MS. We focus on: (i) the role of astrocytes in maintaining the homeostasis and spatial distribution of different secreted cues that determine OPC proliferation, migration, and differentiation during CNS development; (ii) the role of microglia and astrocytes in the redistribution of iron, which is crucial for myelin synthesis during CNS development and for myelin repair in MS; (iii) how microglia secrete different molecules, e.g., growth factors, that favor the recruitment of OPCs in acute phases of MS lesions; and (iv) how astrocytes modify the extraCellular matrix in MS lesions, affecting the ability of OPCs to attempt spontaneous remyelination. Together, these issues demonstrate how both astroglia and microglia influence OPCs in physiological and pathological situations, reinforcing the concept that both development and neural repair are complex and global phenomena. Understanding the molecular and Cellular mechanisms that control OPC survival, proliferation, migration, and differentiation during development, as well as in the mature CNS, may open new opportunities in the search for reparative therapies in demyelinating diseases like MS.
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megalin mediates the influence of sonic hedgehog on Oligodendrocyte Precursor Cell migration and proliferation during development
Glia, 2012Co-Authors: Maria Cristina Ortega, Fernando De Castro, Olivier Cases, Paloma Merchan, Renata Kozyraki, Diego ClementeAbstract:Oligodendrocyte Precursor Cells (OPCs) of the optic nerve are generated in the preoptic area, from where they migrate to colonize it entirely. Sonic hedgehog (Shh) induces the proliferation of these Cells as well as influencing their migration, acting through its canonical receptor (Ptc-1). However, the multiligand receptor megalin (or LRP-2) is also involved in Shh-induced OPC proliferation and migration, and thus, we have evaluated the relevance of this interaction. During the stages at which Shh influences OPC development, we found megalin to be selectively expressed by optic nerve astrocytes, whereas Ptc-1 and Gli1 were found in OPCs. Indeed, this pattern of expression paralleled the rostral–caudal expression of the three Shh-related molecules during the time course of plp-dm20+-OPC colonization. The blockage of megalin partially abolished OPC chemoattraction and fully impaired Shh-induced proliferation. Using in vitro co-cultures of dissociated optic nerve Cells, we demonstrated that Shh was internalized by astrocytes via megalin, and sufficient Shh was subsequently released to produce the biological effects on OPCs observed in the nerve. Together, these data indicate that at least part of the influence of Shh on OPCs is mediated by megalin during optic nerve development, and that astrocytes expressing megalin transiently capture Shh to present it to OPCs and/or to control the gradient of this molecule during development. © 2012 Wiley Periodicals, Inc.
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role of the Cellular prion protein in Oligodendrocyte Precursor Cell proliferation and differentiation in the developing and adult mouse cns
PLOS ONE, 2012Co-Authors: Ana Bribian, Xavier Fontana, Franc Llorens, Rosalina Gavin, Manuel Reina, Jose Manuel Garciaverdugo, Juan Maria Torres, Fernando De Castro, Jose Antonio Del RioAbstract:There are numerous studies describing the signaling mechanisms that mediate Oligodendrocyte Precursor Cell (OPC) proliferation and differentiation, although the contribution of the Cellular prion protein (PrPc) to this process remains unclear. PrPc is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse Cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrPc influences Oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrPc proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of Oligodendrocyte lineage markers. In addition, numerous NG2-positive Cells were observed in cortical regions of adult PrPc knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus Cells.
Charles Ffrenchconstant - One of the best experts on this subject based on the ideXlab platform.
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up regulation of Oligodendrocyte Precursor Cell αv integrin and its extraCellular ligands during central nervous system remyelination
Journal of Neuroscience Research, 2009Co-Authors: Chao Zhao, Robin J M Franklin, Stephen P J Fancy, Charles FfrenchconstantAbstract:To determine the role of extraCellular matrix molecules and their integrin ligands in CNS remyelination, we have examined in experimentally induced focal demyelinated lesions the expression of the two classes of integrins implicated in Oligodendrocyte development and myelination: alpha6 laminin-binding integrins and alphaV integrins that bind a range of extraCellular matrix proteins containing the -Arg-Gly-Asp- (RGD) recognition sequence. Only alphaV integrins were up-regulated during remyelination, being expressed on Oligodendrocyte Precursor Cells during their recruitment into the lesion. Next, therefore, we examined the expression of extraCellular matrix ligands for alphaV integrins and documented increased expression of tenascin-C, tenascin-R, fibronectin, and vitronectin. Taken together with our previous discovery of high levels of expression of another alphaV ligand, osteopontin, during remyelination in these lesions, our findings suggest that alphaV integrins make an important contribution to successful repair in the CNS.
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contrasting effects of mitogenic growth factors on Oligodendrocyte Precursor Cell migration
Glia, 1997Co-Authors: Richard Milner, Richard Reynolds, Robin J M Franklin, Helen Anderson, Rebecca F Rippon, Jennifer S Mckay, Mark A Marchionni, Charles FfrenchconstantAbstract:We have examined the effects of the mitogenic growth factors platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and glial growth factor-2 (GGF-2) on Oligodendrocyte Precursor migration. In an agarose drop migration assay PDGF and bFGF stimulated migration while GGF-2 had no effect. The migration-enhancing effect of bFGF cannot be blocked by neutralising antibodies against PDGF, confirming that this effect is direct and not mediated via upregulation of PDGF receptors. Based on our results, we propose a model in which the differing effects of PDGF and GGF-2 ensure appropriate numbers of Oligodendrocyte Precursor Cells in the vicinity of axons to be myelinated during development.
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tenascin c inhibits Oligodendrocyte Precursor Cell migration by both adhesion dependent and adhesion independent mechanisms
Molecular and Cellular Neuroscience, 1996Co-Authors: B W Kiernan, Bernhard Gotz, Andreas Faissner, Charles FfrenchconstantAbstract:Abstract Tenascin-C is present within the developing central nervous system during Oligodendrocyte Precursor Cell migration. Tenascin-C is antiadhesive for Oligodendrocytes, suggesting a role in controlling the migration of Oligodendrocyte Precursors and hence the pattern of myelination. Here we show directly that tenascin-C is a repulsive (or antiadhesive) substrate for primary Oligodendrocyte Precursors and also inhibits their migration. The antimigratory effect of tenascin-C on oligodendroglia is mediated through two distinct mechanisms; reduced substrate adhesion and a direct inhibition of Cell migration that is independent of adhesion. These two effects map to different domains of the tenascin-C molecule. The repulsive effect maps to the EGF-like repeats and the alternatively spliced FN III repeats while the direct migration-inhibiting effect maps to FN III repeats 7–8. Our results show tenascin-C to have the novel property of inhibiting migration by both adhesion-dependent and adhesion-independent mechanisms, with different regions of the same molecule responsible for the two effects.
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Oligodendrocyte Precursor o 2a progenitor Cell migration a model system for the study of Cell migration in the developing central nervous system
Development, 1993Co-Authors: B W Kiernan, Charles FfrenchconstantAbstract:Cell migration plays an important role in the development of complex multiCellular organisms. The molecular mechanisms that regulate this migration are therefore of great interest. Unfortunately, however, analysis of Cell migration in vertebrates is hampered by the inaccessability of the Cells and the difficulty of manipulating their environment within the embryo. This review focusses on one particular migratory Cell population, the Oligodendrocyte Precursor Cell or 0-2A progenitor Cell, that gives rise to the myelin-forming Oligodendrocytes within the CNS. These Cells migrate extensively during normal development. They can be purified and grown in large numbers in Cell culture, so allowing the use of reductionist approaches using Cell and molecular biology techniques
Brahim Nait-oumesmar - One of the best experts on this subject based on the ideXlab platform.
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The intellectual disability protein PAK3 regulates Oligodendrocyte Precursor Cell differentiation
Neurobiology of Disease, 2017Co-Authors: Majistor Raj Luxman Maglorius Renkilaraj, Lucas Baudouin, Vidjeacoumary Cannaya, Jean-vianney Barnier, Zhengping Jia, C M Wells, Rosine Wehrlé, Mohamed Doulazmi, Corinne Bachelin, Brahim Nait-oumesmarAbstract:Oligodendrocyte and myelin deficits have been reported in mental/psychiatric diseases. The p21-activated kinase 3 (PAK3), a serine/threonine kinase, whose activity is stimulated by the binding of active Rac and Cdc42 GTPases is affected in these pathologies. Indeed, many mutations of Pak3 gene have been described in non-syndromic intellectual disability diseases. Pak3 is expressed mainly in the brain where its role has been investigated in neurons but not in glial Cells. Here, we showed that PAK3 is highly expressed in Oligodendrocyte Precursors (OPCs) and its expression decreases in mature Oligodendrocytes. In the developing white matter of the Pak3 knockout mice, we found defects of Oligodendrocyte differentiation in the corpus callosum and to a lesser extent in the anterior commissure, which were compensated at the adult stage. In vitro experiments in OPC cultures, derived from Pak3 knockout and wild type brains, support a developmental and Cell-autonomous role for PAK3 in regulating OPC differentiation into mature Oligodendrocytes. Moreover, we did not detect any obvious alterations of the proliferation or migration of Pak3 null OPCs compared to wild type. Overall, our data highlight PAK3 as a new regulator of OPC differentiation.
Isidora Paredes - One of the best experts on this subject based on the ideXlab platform.
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Oligodendrocyte Precursor Cell specification is regulated by bidirectional neural progenitor endothelial Cell crosstalk
Nature Neuroscience, 2021Co-Authors: Isidora Paredes, Jose Ricardo Vieira, Bhavin Shah, Carla F Ramunno, Julia Dyckow, Heike Adler, Melanie Richter, Geza Schermann, Evangelia GiannakouriAbstract:Neural-derived signals are crucial regulators of CNS vascularization. However, whether the vasculature responds to these signals by means of elongating and branching or in addition by building a feedback response to modulate neurodevelopmental processes remains unknown. In this study, we identified bidirectional crosstalk between the neural and the vascular compartment of the developing CNS required for Oligodendrocyte Precursor Cell specification. Mechanistically, we show that neural progenitor Cells (NPCs) express angiopoietin-1 (Ang1) and that this expression is regulated by Sonic hedgehog. We demonstrate that NPC-derived Ang1 signals to its receptor, Tie2, on endothelial Cells to induce the production of transforming growth factor beta 1 (TGFβ1). Endothelial-derived TGFβ1, in turn, acts as an angiocrine molecule and signals back to NPCs to induce their commitment toward Oligodendrocyte Precursor Cells. This work demonstrates a true bidirectional collaboration between NPCs and the vasculature as a critical regulator of oligodendrogenesis. Paredes et al. identify bidirectional crosstalk between the neural and the vascular compartment in the developing CNS required for Oligodendrocyte Precursor Cell specification and mediated by an angiopoietin1–Tie2–TGFs1 signaling axis.
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Oligodendrocyte Precursor Cell specification is regulated by bidirectional neural progenitor endothelial Cell crosstalk
Nature Neuroscience, 2021Co-Authors: Isidora Paredes, Jose Ricardo Vieira, Bhavin Shah, Carla F Ramunno, Julia Dyckow, Heike Adler, Melanie Richter, Geza Schermann, Evangelia GiannakouriAbstract:Neural-derived signals are crucial regulators of CNS vascularization. However, whether the vasculature responds to these signals by means of elongating and branching or in addition by building a feedback response to modulate neurodevelopmental processes remains unknown. In this study, we identified bidirectional crosstalk between the neural and the vascular compartment of the developing CNS required for Oligodendrocyte Precursor Cell specification. Mechanistically, we show that neural progenitor Cells (NPCs) express angiopoietin-1 (Ang1) and that this expression is regulated by Sonic hedgehog. We demonstrate that NPC-derived Ang1 signals to its receptor, Tie2, on endothelial Cells to induce the production of transforming growth factor beta 1 (TGFβ1). Endothelial-derived TGFβ1, in turn, acts as an angiocrine molecule and signals back to NPCs to induce their commitment toward Oligodendrocyte Precursor Cells. This work demonstrates a true bidirectional collaboration between NPCs and the vasculature as a critical regulator of oligodendrogenesis.
