|Title:||Olfactory-Experience- and Developmental-Stage-Dependent Control of CPEB4 Regulates c-Fos mRNA Translation for Granule Cell Survival||Authors:||Tseng, Ching San
Chao, Hsu Wen
Huang, Yi Shuian
|Issue Date:||21-Nov-2017||Journal Volume:||21||Journal Issue:||8||Start page/Pages:||2264-2276||Source:||Cell Reports||Abstract:||
© 2017 The Author(s) Mammalian olfactory bulbs (OBs) require continuous replenishment of interneurons (mainly granule cells [GCs]) to support local circuits throughout life. Two spatiotemporally distinct waves of postnatal neurogenesis contribute to expanding and maintaining the GC pool. Although neonate-born GCs have a higher survival rate than adult-born GCs, the molecular mechanism underlying this survival remains unclear. Here, we find that cytoplasmic polyadenylation element-binding protein 4 (CPEB4) acts as a survival factor exclusively for early postnatal GCs. In mice, during the first 2 postnatal weeks, olfactory experience initiated CPEB4-activated c-Fos mRNA translation. In CPEB4-knockout mice, c-FOS insufficiency reduced neurotrophic signaling to impair GC survival and cause OB hypoplasia. Both cyclic AMP responsive element binding protein (CREB)-dependent transcription and CPEB4-promoted translation support c-FOS expression early postnatal OBs but disengage in adult OBs. Activity-related c-FOS synthesis and GC survival are thus developmentally controlled by distinct molecular mechanisms to govern OB growth. Tseng et al. find that olfactory-stimulation- and early-postnatal time-dependent control of CPEB4 activates c-Fos translation for granule cell survival. The authors propose that CPEB4 coordinates with CREB-mediated transcription to increase c-FOS expression, regulation that is lost in adult mice.
|Appears in Collections:||腦與心智科學研究所|
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