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

Nature Neuroscience volume 9, pages 340–348 (2006)Cite this article

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.

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Figure 1: VEGF-C is required for neural development in Xenopus.
Figure 2: The expression of VEGFR-3 and VEGF-C in the embryonic mouse brain.
Figure 3: Proliferative effect of VEGF-C on optic nerve OPCs.
Figure 4: OPCs are severely reduced in the optic nerve of Vegfc-deficient mice.
Figure 5: VEGF-C is required for neurogenesis in the olfactory bulb.

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Acknowledgements

We thank A. Williams, K. Heydon and P. Topilko for critically reading the manuscript and A. Chedotal for discussions. Glivec was provided by Novartis International AG and anti-Sox9 Ab by M. Wegner. This work was supported by Institut National de la Santé et de la Recherche Médicale (INSERM; J.-L.T., B.Z., M.-J.B., A.E.), Ministère de l'éducation nationale, de l'enseignement supérieur et de la recherche (MENESR; A.E., J.-L.T.), European Community (Lymphangiogenomics LSHG-CT-2004-503573 to K.A., P.C., A.E.), the US National Institutes of Health (R01 HL075183-02 to K.A.), the Academy of Finland (K.A., M.J.K.), the Association pour la Recherche de la Sclérose en Plaques (ARSEP) and Association Européenne contre les Leucodystrophies (ELA) (J.-L.T.), Association pour la Recherche sur la Cancer (ARC, A.E.), and the Novo Nordisk Foundation (K.A.). B.L.B was a fellow of MENESR, the Fondation Recherche Médicale (FRM) and the Ligue Française contre la Sclérose En Plaques (LFSEP). L.Y. was supported by Fondation Schlumberger. A.N was sponsored by a Marie Curie Intra-European Fellowship.

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Author notes

  1. Barbara Le Bras and Maria-José Barallobre: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (INSERM), U711, Paris, F-75013, France

    Barbara Le Bras, Maria-José Barallobre, Jihane Homman-Ludiye, Elli Chatzopoulou, Bernard Zalc & Jean-Léon Thomas

  2. Université Pierre & Marie Curie, Faculté de Médecine Pitié Salpêtrière, IFR 70, Paris, F-75005, France

    Barbara Le Bras, Maria-José Barallobre, Jihane Homman-Ludiye, Marie-Paule Muriel, Elli Chatzopoulou, Bernard Zalc & Jean-Léon Thomas

  3. Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, Campus Gasthuisberg, Herestraat 49, Leuven, B-3000, Belgium

    Annelii Ny, Sabine Wyns & Peter Carmeliet

  4. Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, Helsinki, 00014, Finland

    Tuomas Tammela, Paula Haiko, Marika J Karkkainen & Kari Alitalo

  5. INSERM, U36, Paris, F-75005, France

    Li Yuan, Christiane Bréant & Anne Eichmann

  6. Collège de France, 11 Place Marcelin Berthelot, Paris, F-75005, France

    Li Yuan, Christiane Bréant & Anne Eichmann

  7. INSERM, U679, Paris, F-75651, France

    Marie-Paule Muriel

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Supplementary information

Supplementary Fig. 1

VEGF-C requirement for neural development in Xenopus tadpoles. (PDF 631 kb)

Supplementary Fig. 2

VEGFR-3 and VEGF-C expression in the embryonic mouse brain. (PDF 1221 kb)

Supplementary Fig. 3

VEGF-C promotes oligodendrogenesis in the embryonic ventral forebrain. (PDF 248 kb)

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Le Bras, B., Barallobre, MJ., Homman-Ludiye, J. et al. VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nat Neurosci 9, 340–348 (2006). https://doi.org/10.1038/nn1646

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