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

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.

Adult human mesenchymal cells proliferate and migrate in response to chemokines expressed in demyelination

“…Initially, cells were plated at a density of 4 x 10 5 /cm 2 in standard hMSC medium [DMEM supplemented with 10% foetal bovine These experiments are the first to explore the migration of hMSCs using the agarose drop assay which allows for quantitative analysis of migration and assessment of cell morphology in response to changes in culture medium over 72 h, although direction and velocity of migration are not assessed. 21 The results broadly concur with the findings of other investigators who have studied chemokine-induced migration of hMSCs ( Table 1). [22][23][24][25][26][27][28][29][30][31] A notable exception was the failure to demonstrate migration of hMSCs in response to MCP-1 by Ringe et al 26 and CroitoruLamoury et al 22 although the latter did demonstrate chemotaxis following pre-treatment with interferon-β.…”

Hypoxia-Ischemia Induces an Endogenous Reparative Response by Local Neural Progenitors in the Postnatal Mouse Telencephalon

“…First, we demonstrated that HI caused an increase in cells capable of migration both at the presumptive source and at the destination. Following HI injury, we found increased numbers of cells in the SVZ that expressed PDGFR ␣ which is found predominantly in migratory and mitotic OPCs [Rivers et al, 2008;Frost et al, 2009]. We also found increased PDGFR ␣ + cells in the adjacent striatum.…”

“…We used immunofluorescence to probe for PDGFR ␣ in order to characterize changes in OPCs [Rivers et al, 2008;Frost et al, 2009] …”

TAPP1 inhibits the differentiation of oligodendrocyte precursor cells via suppressing the Mek/Erk pathway

“…Several studies have implicated the PI3K/Akt pathway in the proliferation, migration, or survival of OPCs [16][17][18][19][20][21][22] , so we examined the effects of TAPP1 inhibition on the expression of Akt during OPC differentiation. Surprisingly, TAPP1…”