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The Journal of Neuroscience, May 15, 2001, 21(10):3332-3341

Semaphorin 3A-Vascular Endothelial Growth Factor-165 Balance Mediates Migration and Apoptosis of Neural Progenitor Cells by the Recruitment of Shared Receptor

Dominique Bagnard1, Catherine Vaillant1, Seng-Thuon Khuth1, Nathalie Dufay1, Marion Lohrum2, Andreas W. Püschel2, Marie-Françoise Belin1, Jürgen Bolz3, and Nicole Thomasset1

1 Institut National de la Santé et de la Recherche Médicale U433, Neurobiologie Experimentale et Physiopathologie, Faculté de Médecine Laënnec, 69372 Lyon cedex 08, France, 2 Max-Planck-Institut für Hirnforschung, Abt. Neurochemie, Molecular Neurogenetics Laboratory, 60528 Frankfurt, Germany, and 3 Universität Jena, Institut für Allgemeine Zoologie, 07743 Jena, Germany

The dynamic and coordinated interaction between cells and their microenvironment controls cell migration, proliferation, and apoptosis, mediated by different cell surface molecules. We have studied the response of a neuroectodermal progenitor cell line, Dev, to a guidance molecule, semaphorin 3A (Sema3A), described previously as a repellent-collapsing signal for axons, and we have shown that Sema3A acts as a repellent guidance cue for migrating progenitor cells and, on prolonged application, induces apoptosis. Both repulsion and induction of cell death are mediated by neuropilin-1, the ligand-binding component of the Sema3A receptor. The vascular endothelial growth factor, VEGF165, antagonizes Sema3A-induced apoptosis and promotes cell survival, migration, and proliferation. Surprisingly, repulsion by Sema3A also depends on expression of VEGFR1, a VEGF165 receptor, expressed in Dev cells. Moreover, we found that these repulsive effects of Sema3A require tyrosine kinase activity, which can be attributed to VEGFR1. These results indicate that the balance between guidance molecules and angiogenic factors can modulate the migration, apoptosis (or survival), and proliferation of neural progenitor cells through shared receptors.

Key words: apoptosis; semaphorin; VEGF; migration; neuropilin; VEGFR1

Copyright © 2001 Society for Neuroscience  0270-6474/01/21103332-10$05.00/0




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