Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis

Mi Hyeon Jang, Michael A. Bonaguidi, Yasuji Kitabatake, Jiaqi Sun, Juan Song, Eunchai Kang, Heechul Jun, Chun Zhong, Yijing Su, Junjie U. Guo, Marie Xun Wang, Kurt A. Sailor, Ju Young Kim, Yuan Gao, Kimberly M. Christian, Guo Li Ming, Hongjun Song

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Abstract

Adult neurogenesis, the process of generating mature neurons from adult neural stem cells, proceeds concurrently with ongoing neuronal circuit activity and is modulated by various physiological and pathological stimuli. The niche mechanism underlying the activity-dependent regulation of the sequential steps of adult neurogenesis remains largely unknown. Here, we report that neuronal activity decreases the expression of secreted frizzled-related protein 3 (sFRP3), a naturally secreted Wnt inhibitor highly expressed by adult dentate gyrus granule neurons. Sfrp3 deletion activates quiescent radial neural stem cells and promotes newborn neuron maturation, dendritic growth, and dendritic spine formation in the adult mouse hippocampus. Furthermore, sfrp3 reduction is essential for activity-induced adult neural progenitor proliferation and the acceleration of new neuron development. Our study identifies sFRP3 as an inhibitory niche factor from local mature dentate granule neurons that regulates multiple phases of adult hippocampal neurogenesis and suggests an interesting activity-dependent mechanism governing adult neurogenesis via the acute release of tonic inhibition.

Original languageEnglish (US)
Pages (from-to)215-223
Number of pages9
JournalCell Stem Cell
Volume12
Issue number2
DOIs
StatePublished - Feb 7 2013

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ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Jang, M. H., Bonaguidi, M. A., Kitabatake, Y., Sun, J., Song, J., Kang, E., Jun, H., Zhong, C., Su, Y., Guo, J. U., Wang, M. X., Sailor, K. A., Kim, J. Y., Gao, Y., Christian, K. M., Ming, G. L., & Song, H. (2013). Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis. Cell Stem Cell, 12(2), 215-223. https://doi.org/10.1016/j.stem.2012.11.021