title: The neuronal PAS domain protein 3 transcription factor controls FGF-mediated adult hippocampal neurogenesis in mice.
abstract: The neuronal PAS domain protein 3 (NPAS3) gene encoding a brain-enriched transcription factor was recently found to be disrupted in a family suffering from schizophrenia. Mice harboring compound disruptions in the NPAS3 and related NPAS1 genes manifest behavioral and neuroanatomical abnormalities reminiscent of schizophrenia. Herein we demonstrate that Npas3-/- mice are deficient in expression of hippocampal FGF receptor subtype 1 mRNA, most notably in the dentate gyrus. In vivo BrdUrd-labeling shows that basal neural precursor cell proliferation in the dentate gyrus of Npas3-/- mice is reduced by 84% relative to wild-type littermates. We propose that a deficiency in adult neurogenesis may cause the behavioral and neuroanatomical abnormalities seen in Npas3-/- mice, and we speculate that impaired neurogenesis may be involved in the pathophysiology of schizophrenia.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Pieper
authors.forename: Xinle
authors.initials: X
authors.lastname: Wu
authors.forename: Tina W
authors.initials: TW
authors.lastname: Han
authors.forename: Sandi Jo
authors.initials: SJ
authors.lastname: Estill
authors.forename: Quyen
authors.initials: Q
authors.lastname: Dang
authors.forename: Leeju C
authors.initials: LC
authors.lastname: Wu
authors.forename: Sarah
authors.initials: S
authors.lastname: Reece-Fincanon
authors.forename: Carol A
authors.initials: CA
authors.lastname: Dudley
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
authors.forename: Steven L
authors.initials: SL
authors.lastname: McKnight
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000033:anatomy & histology / Q000737:chemistry / Q000166:cytology / Q000254:growth & development; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016222:Fibroblast Growth Factor 2; D012333:RNA, Messenger; C492587:Npas3 protein, mouse