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Initiation of Oligodendrocyte Progenitor Cell Migration by a PDGF-A Activated Extracellular Regulated Kinase (ERK) Signaling Pathway

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Abstract

During CNS development, oligodendrocyte progenitor (OP) cells migrate from germinal zones to presumptive white matter tracts to generate myelinating oligodendrocytes. In vitro and in vivo studies indicate that platelet-derived growth factor-A (PDGF-A) is a potent chemoattractant for OP cells and important for normal distribution throughout the developing CNS. However, PDGF-A does not localize in concentration gradients corresponding to OP migratory pathways, as would be expected for a chemoattractant to direct migration. Therefore, the mechanism by which PDGF-A regulates OP distribution remains to be clarified. Here we show that PDGF-A induces OP migration and continuous exposure to PDGF-A is not required to maintain migration. Using pharmacological inhibitors, we show that a self-sustaining extracellular-regulated-kinase signaling pathway drives OP migration for up to 72 hours after the initial PDGF stimulus. These findings indicate PDGF-A may act to mobilize OP cells that then respond to distinct directional signals to distribute appropriately within the CNS.

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Acknowledgements

This work was supported by National Institutes of Health Grant NS39293 (RCA), National Multiple Sclerosis Society Grant RG3515. (RCA), the Manitoba Children’s Hospital Foundation (EEF) and the Manitoba Health Research Council (EEF). We thank Dr. Joel Levine for reagents, Dr. Mary-Lou Cutler for reagents and helpful discussions. Jan Mustapha for technical assistance, and Dr. Katharine Blaschuk for helpful discussion and critical reading of the manuscript. Mrs. Nina Kelly for administrative assistance.

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Authors and Affiliations

  1. Department of Pathology, University of Manitoba, JBRC401, 727 McDermot Avenue, Winnipeg, MB, Canada, R3E 3P5

    Emma E. Frost, ZhiCheng Zhou & Kimberley Krasnesky

  2. Manitoba Institute of Child Health, Winnipeg, MB, Canada

    Emma E. Frost, ZhiCheng Zhou & Kimberley Krasnesky

  3. Department of Anatomy and Physiology and Genetics, Uniformed Services, University of the Health Sciences, Bethesda, MD, USA

    Regina C. Armstrong

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  1. Emma E. Frost
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  2. ZhiCheng Zhou
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Correspondence to Emma E. Frost.

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Special issue article in honor of Dr. George DeVries.

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Frost, E.E., Zhou, Z., Krasnesky, K. et al. Initiation of Oligodendrocyte Progenitor Cell Migration by a PDGF-A Activated Extracellular Regulated Kinase (ERK) Signaling Pathway. Neurochem Res 34, 169–181 (2009). https://doi.org/10.1007/s11064-008-9748-z

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