A septo-temporal molecular gradient of sfrp3 in the dentate gyrus differentially regulates quiescent adult hippocampal neural stem cell activation

Jiaqi Sun, Michael A. Bonaguidi, Heechul Jun, Junjie U. Guo, Gerald J. Sun, Brett Will, Zhengang Yang, Mi Hyeon Jang, Hongjun Song, Guo Li Ming, Kimberly M. Christian

Research output: Contribution to journalArticle

Abstract

Background: A converging body of evidence indicates that levels of adult hippocampal neurogenesis vary along the septo-temporal axis of the dentate gyrus, but the molecular mechanisms underlying this regional heterogeneity are not known. We previously identified a niche mechanism regulating proliferation and neuronal development in the adult mouse dentate gyrus resulting from the activity-regulated expression of secreted frizzled-related protein 3 (sfrp3) by mature neurons, which suppresses activation of radial glia-like neural stem cells (RGLs) through inhibition of Wingless/INT (WNT) protein signaling. Results: Here, we show that activation rates within the quiescent RGL population decrease gradually along the septo-temporal axis in the adult mouse dentate gyrus, as defined by MCM2 expression in RGLs. Using in situ hybridization and quantitative real-time PCR, we identified an inverse septal-to-temporal increase in the expression of sfrp3 that emerges during postnatal development. Elimination of sfrp3 and its molecular gradient leads to increased RGL activation, preferentially in the temporal region of the adult dentate gyrus. Conclusions: Our study identifies a niche mechanism that contributes to the graded distribution of neurogenesis in the adult dentate gyrus and has important implications for understanding functional differences associated with adult hippocampal neurogenesis along the septo-temporal axis.

Original languageEnglish (US)
Article number52
JournalMolecular Brain
Volume8
Issue number1
DOIs
StatePublished - Sep 4 2015

Fingerprint

Neural Stem Cells
Dentate Gyrus
Neurogenesis
Population Dynamics
Temporal Lobe
Neuroglia
In Situ Hybridization
Real-Time Polymerase Chain Reaction
frizzled related protein-3
Neurons
Proteins

Keywords

  • Adult hippocampal neurogenesis
  • Molecular gradient
  • neural stem cells
  • niche
  • Septo-temporal axis
  • Wnt

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology

Cite this

A septo-temporal molecular gradient of sfrp3 in the dentate gyrus differentially regulates quiescent adult hippocampal neural stem cell activation. / Sun, Jiaqi; Bonaguidi, Michael A.; Jun, Heechul; Guo, Junjie U.; Sun, Gerald J.; Will, Brett; Yang, Zhengang; Jang, Mi Hyeon; Song, Hongjun; Ming, Guo Li; Christian, Kimberly M.

In: Molecular Brain, Vol. 8, No. 1, 52, 04.09.2015.

Research output: Contribution to journalArticle

Sun, J, Bonaguidi, MA, Jun, H, Guo, JU, Sun, GJ, Will, B, Yang, Z, Jang, MH, Song, H, Ming, GL & Christian, KM 2015, 'A septo-temporal molecular gradient of sfrp3 in the dentate gyrus differentially regulates quiescent adult hippocampal neural stem cell activation', Molecular Brain, vol. 8, no. 1, 52. https://doi.org/10.1186/s13041-015-0143-9
Sun, Jiaqi ; Bonaguidi, Michael A. ; Jun, Heechul ; Guo, Junjie U. ; Sun, Gerald J. ; Will, Brett ; Yang, Zhengang ; Jang, Mi Hyeon ; Song, Hongjun ; Ming, Guo Li ; Christian, Kimberly M. / A septo-temporal molecular gradient of sfrp3 in the dentate gyrus differentially regulates quiescent adult hippocampal neural stem cell activation. In: Molecular Brain. 2015 ; Vol. 8, No. 1.
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