The neuronal PAS domain protein 3 transcription factor controls FGF-mediated adult hippocampal neurogenesis in mice.
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.
Pieper
Andrew A
AA
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Wu
Xinle
X
Han
Tina W
TW
Estill
Sandi Jo
SJ
Dang
Quyen
Q
Wu
Leeju C
LC
Reece-Fincanon
Sarah
S
Dudley
Carol A
CA
Richardson
James A
JA
Brat
Daniel J
DJ
McKnight
Steven L
SL
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
D051792:Basic Helix-Loop-Helix Proteins; D016222:Fibroblast Growth Factor 2; D012333:RNA, Messenger; C492587:Npas3 protein, mouse