The neuronal PAS domain protein 3 transcription factor controls FGF-mediated adult hippocampal neurogenesis in mice

Andrew A. Pieper, Xinle Wu, Tina W. Han, Sandi Jo Estill, Quyen Dang, Leeju C. Wu, Sarah Reece-Fincanon, Carol A. Dudley, James A. Richardson, Daniel J. Brat, Steven L. McKnight

Research output: Contribution to journalArticle

107 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)14052-14057
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number39
DOIs
StatePublished - Sep 27 2005

Keywords

  • Electroconvulsive seizure
  • Fibroblast growth factor
  • Hippocampus
  • Schizophrenia
  • Sprouty4

ASJC Scopus subject areas

  • General

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