title: Oncostatin M regulates neural precursor activity in the adult brain.
abstract: 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, OsmRβ, 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 OsmRβ 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.
authors.affiliation: The Queensland Brain Institute, The University of Queensland, Brisbane QLD 4072, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Beatus
authors.forename: Dhanisha J
authors.initials: DJ
authors.lastname: Jhaveri
authors.forename: Tara L
authors.initials: TL
authors.lastname: Walker
authors.forename: Peter G
authors.initials: PG
authors.lastname: Lucas
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Rietze
authors.forename: Helen M
authors.initials: HM
authors.lastname: Cooper
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Perry F
authors.initials: PF
authors.lastname: Bartlett
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D005434:Flow Cytometry; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053683:Oncostatin M / Q000378:metabolism* / Q000494:pharmacology; D053681:Oncostatin M Receptor beta Subunit / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D053681:Oncostatin M Receptor beta Subunit; C508352:Osm protein, mouse; D053683:Oncostatin M