Initiation of oligodendrocyte progenitor cell migration by a PDGF-A activated extracellular regulated kinase (ERK) signaling pathway.
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.
Department of Pathology, University of Manitoba, JBRC401, 727 McDermot Avenue, Winnipeg, MB, Canada, R3E 3P5. froste@cc.umanitoba.ca
Emma E
EE
Frost
Zhicheng
Z
Zhou
Kimberley
K
Krasnesky
Regina C
RC
Armstrong
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D025461:Feedback, Physiological; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D054467:Phospholipases A2 / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054467:Phospholipases A2