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| Wnt signalling regulates adult hippocampal neurogenesis |
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| Author(s): Lie DC, Colamarino SA, Song HJ, Desire L, Mira H, Consiglio A, Lein ES, Jessberger S, Lansford H, Dearie AR, Gage FH |
| Source: NATURE Volume: 437 Issue: 7063 Pages: 1370-1375 Published: OCT 27 2005 |
| Times Cited: 223 References: 27 |
| Abstract: The generation of new neurons from neural stem cells is restricted to two regions of the adult mammalian central nervous system: the subventricular zone of the lateral ventricle, and the subgranular zone of the hippocampal dentate gyrus(1). In both regions, signals provided by the microenvironment regulate the maintenance, proliferation and neuronal fate commitment of the local stem cell population(1). The identity of these signals is largely unknown. Here we show that adult hippocampal stem/progenitor cells (AHPs) express receptors and signalling components for Wnt proteins, which are key regulators of neural stem cell behaviour in embryonic development(2). We also show that the Wnt/beta-catenin pathway is active and that Wnt3 is expressed in the hippocampal neurogenic niche. Overexpression of Wnt3 is sufficient to increase neurogenesis from AHPs in vitro and in vivo. By contrast, blockade of Wnt signalling reduces neurogenesis from AHPs in vitro and abolishes neurogenesis almost completely in vivo. Our data show that Wnt signalling is a principal regulator of adult hippocampal neurogenesis and provide evidence that Wnt proteins have a role in adult hippocampal function. |
| Document Type: Article |
| Language: English |
| Reprint Address: Gage, FH (reprint author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA |
Addresses:
1. Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
2. GSF Natl Res Ctr Environm & Hlth, Inst Dev Genet, D-85764 Neuherberg, Germany
3. Johns Hopkins Univ, Sch Med, Dept Neurol, Inst Cell Engn, Baltimore, MD 21205 USA
4. Johns Hopkins Univ, Sch Med, Dept Neurosci, Inst Cell Engn, Baltimore, MD 21205 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 977UQ |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature04108 |
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