Journal
DEVELOPMENTAL NEUROBIOLOGY
Volume 71, Issue 7, Pages 619-633Publisher
WILEY-BLACKWELL
DOI: 10.1002/dneu.20871
Keywords
neural stem cells; cytokines; hippocampus; proliferation; neurogenesis; neurospheres
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Funding
- Australian National Health and Medical Research Council
- Australian Research Council
- Swedish Cancer Society
- Human Frontiers Science Program
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The regulation of neural precursor cell (NPC) activity is the major determinant of the rate of neuronal production in neurogenic regions of the adult brain. Here, we show that Oncostatin M(Osm) and its receptor, OsmR beta, are both expressed in the subventricular zone (SVZ) and that in contradistinction to leukemia inhibitory factor and ciliary neutrophic factor, Osm directly inhibits the proliferation of adult NPCs as measured by a decreased level of neurosphere formation in vitro. Similarly, intraventricular infusion of Osm dramatically decreases the pool of NPCs in both the SVZ and the hippocampus. In keeping with the inhibitory action of Osm, we reveal that mice lacking OsmR beta have substantially more NPCs in the SVZ, the hippocampus and the olfactory bulb, demonstrating that endogenous Osm signaling is important for NPC homeostasis. Finally, we show that Osm can also inhibit clonal growth of glioblastoma-derived neurospheres, further supporting the close link between NPCs and tumor stem cells. (c) 2011 Wiley Periodicals, Inc. Develop Neurobiol 71: 619-633, 2011
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