Abstract
Neuronal and vascular cells share common chemical signals. Vascular endothelial growth factor (VEGF)-C and -D and their receptor VEGFR-3/Flt-4 mediate lymphangiogenesis, but they occur also in the brain. Quantitative RT-PCR of mouse brain tissues and cultivated cells showed that the VEGFR-3 gene is highest transcribed in postnatal brain and in glial precursor cells whereas VEGF-C and -D are variably produced by different neuronal and glial cells. In neurospheres (neural stem cells) VEGFR-3 was induced by differentiation with platelet-derived growth factor (PDGF). In functional studies with an A2B5- and nestin-positive, O4-negative murine glial precursor cell line, VEGF-C and -D stimulated phosphorylation of the kinases Erk1/2; this signal transduction was inhibited by UO126. Both peptides induced the proliferation of glial precursor cells which could be inhibited by UO126. Furthermore, VEGF-D considerably enhanced their migration into an open space in a wound-healing assay. These results show that VEGF-C/-D together with its receptor VEGFR-3 provides an auto-/paracrine growth and chemotactic system for glial precursors in the developing brain.
MeSH terms
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Animals
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Animals, Newborn
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Butadienes / pharmacology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Line
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Chemotaxis / drug effects
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Chemotaxis / physiology
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Enzyme Inhibitors / pharmacology
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Mice
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Mice, Inbred C57BL
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Mitogen-Activated Protein Kinase 3 / drug effects
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Mitogen-Activated Protein Kinase 3 / metabolism
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Neuroglia / drug effects
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Neuroglia / metabolism*
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Nitriles / pharmacology
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Paracrine Communication / drug effects
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Paracrine Communication / physiology
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Phosphorylation / drug effects
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Platelet-Derived Growth Factor / pharmacology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Spheroids, Cellular
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Stem Cells / drug effects
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Stem Cells / metabolism*
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Vascular Endothelial Growth Factor D / metabolism
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Vascular Endothelial Growth Factor D / pharmacology
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Vascular Endothelial Growth Factor Receptor-1 / drug effects
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Vascular Endothelial Growth Factor Receptor-1 / metabolism*
Substances
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Butadienes
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Enzyme Inhibitors
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Nitriles
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Platelet-Derived Growth Factor
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U 0126
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Vascular Endothelial Growth Factor D
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platelet-derived growth factor A
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Vascular Endothelial Growth Factor Receptor-1
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Mitogen-Activated Protein Kinase 3