摘要
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.
原文 | 英語 |
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頁(從 - 到) | 2264-2276 |
頁數 | 13 |
期刊 | Cell Reports |
卷 | 21 |
發行號 | 8 |
DOIs | |
出版狀態 | 已發佈 - 11月 21 2017 |
ASJC Scopus subject areas
- 生物化學、遺傳與分子生物學 (全部)