Olfactory-Experience- and Developmental-Stage-Dependent Control of CPEB4 Regulates c-Fos mRNA Translation for Granule Cell Survival

Ching San Tseng, Hsu Wen Chao, Hsien Sung Huang, Yi Shuian Huang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2264-2276
Number of pages13
JournalCell Reports
Volume21
Issue number8
DOIs
Publication statusPublished - Nov 21 2017

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Keywords

  • BDNF
  • c-Fos mRNA translation
  • cell survival
  • CPEB4
  • CREB
  • granule cell
  • local neurogenesis
  • olfactory bulb

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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