VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain.
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.
Le Bras
Barbara
B
Institut National de la Santé et de la Recherche Médicale (INSERM), U711, Paris F-75013, France.
Barallobre
Maria-José
MJ
Homman-Ludiye
Jihane
J
Ny
Annelii
A
Wyns
Sabine
S
Tammela
Tuomas
T
Haiko
Paula
P
Karkkainen
Marika J
MJ
Yuan
Li
L
Muriel
Marie-Paule
MP
Chatzopoulou
Elli
E
Bréant
Christiane
C
Zalc
Bernard
B
Carmeliet
Peter
P
Alitalo
Kari
K
Eichmann
Anne
A
Thomas
Jean-Léon
JL
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D019143:Evolution, Molecular; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007814:Larva; D020547:Lateral Ventricles / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D009900:Optic Nerve / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D014982:Xenopus laevis
D007381:Intermediate Filament Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3