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      VEGF is a chemoattractant for FGF-2–stimulated neural progenitors

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          Abstract

          Mmigration of undifferentiated neural progenitors is critical for the development and repair of the nervous system. However, the mechanisms and factors that regulate migration are not well understood. Here, we show that vascular endothelial growth factor (VEGF)-A, a major angiogenic factor, guides the directed migration of neural progenitors that do not display antigenic markers for neuron- or glia-restricted precursor cells. We demonstrate that progenitor cells express both VEGF receptor (VEGFR) 1 and VEGFR2, but signaling through VEGFR2 specifically mediates the chemotactic effect of VEGF. The expression of VEGFRs and the chemotaxis of progenitors in response to VEGF require the presence of fibroblast growth factor 2. These results demonstrate that VEGF is an attractive guidance cue for the migration of undifferentiated neural progenitors and offer a mechanistic link between neurogenesis and angiogenesis in the nervous system.

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          Neuronal replacement from endogenous precursors in the adult brain after stroke.

          Andreas Arvidsson, Tove Collin, Deniz Kirik … (2002)
          In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans.
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            Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo.

            Kunlin Jin, Yonghua Zhu, Yunjuan Sun … (2002)
            Vascular endothelial growth factor (VEGF) is an angiogenic protein with neurotrophic and neuroprotective effects. Because VEGF promotes the proliferation of vascular endothelial cells, we examined the possibility that it also stimulates the proliferation of neuronal precursors in murine cerebral cortical cultures and in adult rat brain in vivo. VEGF (>10 ng/ml) stimulated 5-bromo-2'-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20-30%. Cultured cells labeled by BrdUrd expressed VEGFR2/Flk-1, but not VEGFR1/Flt-1 receptors, and the effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. Intracerebroventricular administration of VEGF into rat brain increased BrdUrd labeling of cells in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), where VEGFR2/Flk-1 was colocalized with the immature neuronal marker, doublecortin (Dcx). The increase in BrdUrd labeling after the administration of VEGF was caused by an increase in cell proliferation, rather than a decrease in cell death, because VEGF did not reduce caspase-3 cleavage in SVZ or SGZ. Cells labeled with BrdUrd after VEGF treatment in vivo include immature and mature neurons, astroglia, and endothelial cells. These findings implicate the angiogenesis factor VEGF in neurogenesis as well.
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              Vascular niche for adult hippocampal neurogenesis.

              Theo Palmer, Andrew R. Willhoite, Fred Gage (2000)
              The thin lamina between the hippocampal hilus and granule cell layer, or subgranule zone (SGZ), is an area of active proliferation within the adult hippocampus known to generate new neurons throughout adult life. Although the neuronal fate of many dividing cells is well documented, little information is available about the phenotypes of cells in S-phase or how the dividing cells might interact with neighboring cells in the process of neurogenesis. Here, we make the unexpected observation that dividing cells are found in dense clusters associated with the vasculature and roughly 37% of all dividing cells are immunoreactive for endothelial markers. Most of the newborn endothelial cells disappear over several weeks, suggesting that neurogenesis is intimately associated with a process of active vascular recruitment and subsequent remodeling. The present data provide the first evidence that adult neurogenesis occurs within an angiogenic niche. This environment may provide a novel interface where mesenchyme-derived cells and circulating factors influence plasticity in the adult central nervous system. Copyright 2000 Wiley-Liss, Inc.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cell Biol
                Title: The Journal of Cell Biology
                Publisher: The Rockefeller University Press
                ISSN (Print): 0021-9525
                ISSN (Electronic): 1540-8140
                Publication date (Print): 22 December 2003
                Volume: 163
                Issue: 6
                Pages: 1375-1384
                Affiliations
                [1 ]Department of Morphology, University Medical Center, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland
                [2 ]Department of Anesthesiology, Pharmacology and Surgical Intensive Care, University Hospital of Geneva, CH-1211 Geneva, Switzerland
                Author notes

                Address correspondence to J.Z. Kiss, Dept. of Morphology, University Medical Center, University of Geneva Medical School, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland. Tel.: 41-22-3795202. Fax: 41-22-3795260. email: Jozsef.Kiss@ 123456medecine.unige.ch

                Article
                Publisher ID: 200308040
                DOI: 10.1083/jcb.200308040
                PMC ID: 2173724
                PubMed ID: 14691144
                SO-VID: a6e00d55-b27b-49d9-8bff-36c306a0aeae
                Copyright © Copyright © 2003, The Rockefeller University Press
                History
                Date received : 7 August 2003
                Date accepted : 28 October 2003
                Categories
                Subject: Article

                ScienceOpen disciplines: Cell biology
                Keywords: vegf receptors; live cell microscopy; directional guidance; cell motility; fgf-2
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: vegf receptors; live cell microscopy; directional guidance; cell motility; fgf-2

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