ERK-dependent and -independent pathways trigger human neural progenitor cell migration

Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural m...

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Veröffentlicht in:Toxicology and applied pharmacology 2007-05, Vol.221 (1), p.57-67
Hauptverfasser: Moors, Michaela, Cline, Jason E., Abel, Josef, Fritsche, Ellen
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creator Moors, Michaela
Cline, Jason E.
Abel, Josef
Fritsche, Ellen
description Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways.
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Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>17445854</pmid><doi>10.1016/j.taap.2007.02.018</doi><tpages>11</tpages></addata></record>
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subjects 60 APPLIED LIFE SCIENCES
ACETATES
APOPTOSIS
Astrocytes - cytology
Astrocytes - drug effects
Astrocytes - metabolism
Biological and medical sciences
Blotting, Western
BRAIN
Cell Differentiation - drug effects
Cell Movement - drug effects
Cell Movement - physiology
Cell Survival - drug effects
Cells, Cultured
EGFR
ERK1/2
ETHANOL
Flavonoids - pharmacology
GENE REGULATION
GROWTH FACTORS
HUMAN POPULATIONS
Humans
Indoles - pharmacology
Maleimides - pharmacology
Medical sciences
Methylmercury Compounds - pharmacology
Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 - metabolism
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Neural migration
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
Normal human neural progenitor cells
PHOSPHORYLATION
Phosphorylation - drug effects
PHOSPHOTRANSFERASES
PKC
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - metabolism
Pyrimidines - pharmacology
Quinazolines
RECEPTORS
Signal Transduction - drug effects
Signal Transduction - physiology
Spheroids, Cellular - cytology
Spheroids, Cellular - drug effects
Spheroids, Cellular - metabolism
src
src-Family Kinases - antagonists & inhibitors
src-Family Kinases - metabolism
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
Sulfonamides - pharmacology
Tetradecanoylphorbol Acetate - pharmacology
Toxicology
Tyrphostins - pharmacology
title ERK-dependent and -independent pathways trigger human neural progenitor cell migration
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