The Role of Cytoplasmic Polyadenylation Element Binding Protein 4 in the Regulation of Early Postnatal Neurogenesis and Olfactory Bulb Development

• Main Authors: TSENG, CHING-SAN, 曾慶三
• Other Authors: HUANG, YI-SHUIAN
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/m548h7

博士 === 國防醫學院 === 生命科學研究所 === 106 === 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 show higher survival rate than adult-born GCs, the molecular mechanism underlying this survival remains unclear. Here, we identify RNA-binding protein cytoplasmic polyadenylation element-binding protein 4 (CPEB4) as a survival factor exclusively for early postnatal GCs. During the first 2 postnatal weeks, olfactory experience initiated CPEB4-activated c-Fos mRNA translation. In CPEB4-deficient OBs, c-FOS insufficiency reduced the neurotrophic signaling to impair GC survival and consequently led to OB hypoplasia and defective odor discrimination. Both cyclic AMP responsive element binding protein (CREB)-dependent transcription and CPEB4-promoted translation support c-FOS expression early postnatally but disengage in adult OBs. Activity-related c-FOS synthesis and GC survival is thus developmentally controlled by distinct molecular mechanisms to govern OB growth.