Abstract
Vascular endothelial growth factor C (VEGF-C) was first identified as a regulator of the vascular system, where it is required for the development of lymphatic vessels. Here we report actions of VEGF-C in the central nervous system. We detected the expression of the VEGF-C receptor VEGFR-3 in neural progenitor cells in Xenopus laevis and mouse embryos. In Xenopus tadpole VEGF-C knockdowns and in mice lacking Vegfc, the proliferation of neural progenitors expressing VEGFR-3 was severely reduced, in the absence of intracerebral blood vessel defects. In addition, Vegfc-deficient mouse embryos showed a selective loss of oligodendrocyte precursor cells (OPCs) in the embryonic optic nerve. In vitro, VEGF-C stimulated the proliferation of OPCs expressing VEGFR-3 and nestin-positive ventricular neural cells. VEGF-C thus has a new, evolutionary conserved function as a growth factor selectively required by neural progenitor cells expressing its receptor VEGFR-3.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Animals
- Brain / cytology
- Brain / embryology*
- Brain / metabolism
- Cell Differentiation / physiology*
- Cells, Cultured
- Evolution, Molecular
- Intermediate Filament Proteins / metabolism
- Larva
- Lateral Ventricles / cytology
- Lateral Ventricles / embryology
- Lateral Ventricles / metabolism
- Mice
- Mice, Knockout
- Mice, Transgenic
- Nerve Growth Factors / metabolism*
- Nerve Tissue Proteins / metabolism
- Nestin
- Neurons / cytology
- Neurons / metabolism*
- Oligodendroglia / cytology
- Oligodendroglia / metabolism
- Optic Nerve / cytology
- Optic Nerve / embryology
- Optic Nerve / metabolism
- Rats
- Rats, Wistar
- Stem Cells / cytology
- Stem Cells / metabolism*
- Vascular Endothelial Growth Factor C / genetics
- Vascular Endothelial Growth Factor C / metabolism*
- Vascular Endothelial Growth Factor Receptor-3 / metabolism
- Xenopus laevis
Substances
- Intermediate Filament Proteins
- Nerve Growth Factors
- Nerve Tissue Proteins
- Nes protein, mouse
- Nes protein, rat
- Nestin
- Vascular Endothelial Growth Factor C
- Vascular Endothelial Growth Factor Receptor-3