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Intracellular Signaling Mechanisms Directing Oligodendrocyte Precursor Cell Migration

Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 01/2009; 28(50):13365-7. DOI: 10.1523/JNEUROSCI.4931-08.2008
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    • "The activation of the ERK1 / 2 MAPK pathway by FGF2 and anosmin - 1 , via FGFR1 , is necessary to promote their che - motropic effect on rat SVZ neuroblasts ( Esteban et al . , 2013 ) , but the intracellular signaling controlling OPC migration is poorly understood ( Rajasekharan , 2008 ) . To investigate the FGFR1 downstream signaling involved in the chemotropic effect elicited by FGF2 and anosmin - 1 on rat and mouse corti - cal OPCs , we performed chemotaxis assays using U0126 , a specific inhibitor of the ERK1 / 2 MAPK pathway . "
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    ABSTRACT: Signaling through fibroblast growth factor receptors (FGFRs) is essential for many cellular processes including proliferation and migration, as well as differentiation events such as myelination. Anosmin-1 is an extracellular matrix (ECM) glycoprotein that interacts with the fibroblast growth factor receptor 1 (FGFR1) to exert its biological actions through this receptor, although the intracellular pathways underlying anosmin-1 signaling remain largely unknown. This protein is defective in the X-linked form of Kallmann syndrome (KS) and has a prominent role in the migration of neuronal and oligodendroglial precursors. We have shown that anosmin-1 exerts a chemotactic effect via FGFR1 on neuronal precursors from the subventricular zone (SVZ) and the essential role of the ERK1/2 signaling. We report here the positive chemotactic effect of FGF2 and anosmin-1 on rat and mouse postnatal OPCs via FGFR1. The same effect was observed with the truncated N-terminal region of anosmin-1 (A1Nt). The introduction in anosmin-1 of the missense mutation F517L found in patients suffering from KS annulled the chemotactic activity; however, the mutant form carrying the disease-causing mutation E514K also found in KS patients, behaved as the wild-type protein. The chemoattraction exhibited by FGF2 and anosmin-1 on OPCs was blocked by the mitogen-activated protein kinase (MAPK) inhibitor U0126, suggesting that the activation of the ERK1/2 MAPK signaling pathway following interaction with the FGFR1 is necessary for FGF2 and anosmin-1 to exert their chemotactic effect. In fact, both proteins were able to induce the phosphorylation of the ERK1/2 kinases after the activation of the FGFR1 receptor. GLIA 2013.
    Glia 03/2014; 62(3). DOI:10.1002/glia.22609 · 6.03 Impact Factor
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    • "During development, postmitotic cells of the CNS including neurons and myelin-forming oligodendrocytes migrate from the germinal areas of the neural tube to their final destination sites [30]–[32]. The cellular and molecular bases of OPCs migration during development have been established [33]. "
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    ABSTRACT: We have recently established a culture system to study the impact of simulated microgravity on oligodendrocyte progenitor cells (OPCs) development. We subjected mouse and human OPCs to a short exposure of simulated microgravity produced by a 3D-Clinostat robot. Our results demonstrate that rodent and human OPCs display enhanced and sustained proliferation when exposed to simulated microgravity as assessed by several parameters, including a decrease in the cell cycle time. Additionally, OPC migration was examined in vitro using time-lapse imaging of cultured OPCs. Our results indicated that OPCs migrate to a greater extent after stimulated microgravity than in normal conditions, and this enhanced motility was associated with OPC morphological changes. The lack of normal gravity resulted in a significant increase in the migration speed of mouse and human OPCs and we found that the average leading process in migrating bipolar OPCs was significantly longer in microgravity treated cells than in controls, demonstrating that during OPC migration the lack of gravity promotes leading process extension, an essential step in the process of OPC migration. Finally, we tested the effect of simulated microgravity on OPC differentiation. Our data showed that the expression of mature oligodendrocyte markers was significantly delayed in microgravity treated OPCs. Under conditions where OPCs were allowed to progress in the lineage, simulated microgravity decreased the proportion of cells that expressed mature markers, such as CC1 and MBP, with a concomitant increased number of cells that retained immature oligodendrocyte markers such as Sox2 and NG2. Development of methodologies aimed at enhancing the number of OPCs and their ability to progress on the oligodendrocyte lineage is of great value for treatment of demyelinating disorders. To our knowledge, this is the first report on the gravitational modulation of oligodendrocyte intrinsic plasticity to increase their progenies.
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    ABSTRACT: Constructing fuzzy measures in systems is an important topic in system research. Revising a set function to be a desirable fuzzy measure is one of the practicable strategies of the construction. In this paper, the following fitting problem is investigated: given a universal set and a set function, which is not necessarily a λ-fuzzy measure, defined on a class of subsets of the universal set, we want to find a regular λ-fuzzy measure on the power set of the universal set such that it is as close as possible to the original set function. This is, essentially, an optimization problem. A genetic algorithm is used to search the optimal solution. As a special case, when the set function is already a regular λ-fuzzy measure on the original domain that is a proper subclass of the power set we can obtain a regular λ-fuzzy measure extension on the power set
    Fuzzy Systems, 1996., Proceedings of the Fifth IEEE International Conference on; 10/1996
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