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

Mi-Hyeon Jang* (Corresponding Author), 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)


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
Pages (from-to)215-223
Number of pages9
JournalCell Stem Cell
Issue number2
Publication statusPublished - 7 Feb 2013
Externally publishedYes

Bibliographical note

We thank Drs. D. Ginty, S. Jessberger, X. He, and members of the Song and Ming laboratories for their suggestions, A. Rattner and J. Nathans for generating sfrp3 KO mice, J.H. Shin and B. Xie for help with RNA-seq, and P. Worley for Arc antibodies and initial help with ECS. This work was supported by the NIH (NS047344, MH087874, and ES021957 to H.S; NS048271 and HD069184 to G.M.; MH090115 to M.-H.J.; and NS080913 to M.A.B) and NARSAD (Independent Investigator awards to H.S. and G.-l.M., and a Young Investigator award to M.-H.J.) and by postdoctoral fellowship awards from MSCRF to J.S., E.K., Y.S., and K.C.
Copyright © 2013 Elsevier Inc. All rights reserved.


Dive into the research topics of 'Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis'. Together they form a unique fingerprint.

Cite this