VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain

Nat Neurosci. 2006 Mar;9(3):340-8. doi: 10.1038/nn1646. Epub 2006 Feb 5.

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