VEGFR-3/Flt-4 mediates proliferation and chemotaxis in glial precursor cells.
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.
Kranich
Sandra
S
Department of Anatomy, University of Kiel, Olshausenstrasse 40, 24098 Kiel, Germany.
Hattermann
Kirsten
K
Specht
Aljona
A
Lucius
Ralph
R
Mentlein
Rolf
R
D000818:Animals; D000831:Animals, Newborn; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018874:Spheroids, Cellular; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000187:drug effects / Q000378:metabolism*
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D010982:Platelet-Derived Growth Factor; C113580:U 0126; D042643:Vascular Endothelial Growth Factor D; C075278:platelet-derived growth factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D048052:Mitogen-Activated Protein Kinase 3