Secreted Frizzled-Related Protein 3 Regulates Activity-Dependent Adult Hippocampal Neurogenesis

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• 作者：Mi-Hyeon Jang¹ ; ² ; ⁵ ; ⁸ ; ^{jang.mihyeon@mayo.edu} ; Michael A. Bonaguidi¹ ; ² ; ⁸ ; Yasuji Kitabatake¹ ; ² ; ⁶ ; ⁸ ; Jiaqi Sun¹ ; ⁷ ; ⁸ ; Juan Song¹ ; ² ; Eunchai Kang¹ ; ² ; Heechul Jun¹ ; ⁵ ; Chun Zhong¹ ; ² ; Yijing Su¹ ; ² ; Junjie U. Guo¹ ; ³ ; Marie Xun Wang¹ ; Kurt A. Sailor¹ ; ³ ; Ju-Young Kim¹ ; ² ; Yuan Gao¹ ; ⁴ ; Kimberly M. Christian¹ ; ² ; Guo-li Ming¹ ; ² ; ³ ; Hongjun Song¹ ; ² ; ³ ; ^{shongju1@jhmi.edu}
• 刊名：Cell Stem Cell
• 出版年：2013
• 出版时间：7 February, 2013
• 年：2013
• 卷：12
• 期：2
• 页码：215-223
• 全文大小：1010 K

文摘

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Summary

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.