Dr. Huang, Yi-Shuian 黃怡萱 博士



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

Cell Reports, Nov 21, 2017

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.

Figure Legend:
Tseng et al. show CPEB4 promotes the granule cell survival in the early postnatal olfactory bulb in response to olfactory stimulation. Neonate-born CPEB4-postive cells (in shades of green) outcompete CPEB4-negative cells (in shades of red) in survival to bipolar granule cells. Flowers symbolize olfactory sensory input to initiate CPEB4-regulated survival mechanism.
Artwork by Carol Yang (楊林)



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