title: RNA-binding protein FXR2 regulates adult hippocampal neurogenesis by reducing Noggin expression.
abstract: In adult mammalian brains, neurogenesis persists in the subventricular zone of the lateral ventricles (SVZ) and the dentate gyrus (DG) of the hippocampus. Although evidence suggest that adult neurogenesis in these two regions is subjected to differential regulation, the underlying mechanism is unclear. Here, we show that the RNA-binding protein FXR2 specifically regulates DG neurogenesis by reducing the stability of Noggin mRNA. FXR2 deficiency leads to increased Noggin expression and subsequently reduced BMP signaling, which results in increased proliferation and altered fate specification of neural stem/progenitor cells in DG. In contrast, Noggin is not regulated by FXR2 in the SVZ, because Noggin expression is restricted to the ependymal cells of the lateral ventricles, where FXR2 is not expressed. Differential regulation of SVZ and DG stem cells by FXR2 may be a key component of the mechanism that governs the different neurogenic processes in these two adult germinal zones.
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
authors.forename: Weixiang
authors.initials: W
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Devin M
authors.initials: DM
authors.lastname: Christopher
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Teng
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Fausett
authors.forename: Changmei
authors.initials: C
authors.lastname: Liu
authors.forename: Olivia L
authors.initials: OL
authors.lastname: George
authors.forename: John
authors.initials: J
authors.lastname: Klingensmith
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000941:Antigens; D000943:Antigens, Differentiation / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D047468:Immunoprecipitation / Q000379:methods; D020547:Lateral Ventricles / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4; D000099176:Noggin Protein
chemical_list: D000941:Antigens; D000943:Antigens, Differentiation; D055396:Bone Morphogenetic Protein 2; D002352:Carrier Proteins; D003609:Dactinomycin; D009414:Nerve Growth Factors; D011500:Protein Synthesis Inhibitors; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C512309:FXR2 protein, mouse; C036505:oligodendrocyte O antigen, mouse