Role of C/EBPβ Transcription Factor in Adult Hippocampal Neurogenesis

Background: The dentate gyrus of the hippocampus is one of the regions in which neurogenesis takes place in the adult brain. We have previously demonstrated that CCAAT/enhancer binding protein beta (C/EBP beta) is expressed in the granular layer of the dentate gyrus of the adult mouse hippocampus. Taking into account the important role of C/EBP beta in the consolidation of long term memory, the fact that newborn neurons in the hippocampus contribute to learning and memory processes, and the role of this transcription factor, previously demonstrated by our group, in regulating neuronal differentiation, we speculated that this transcription factor could regulate stem/progenitor cells in this region of the brain. Methodology/Principal Findings: Here, we show, using C/EBP beta knockout mice, that C/EBP beta expression is observed in the subset of newborn cells that proliferate in the hippocampus of the adult brain. Mice lacking C/EBP beta present reduced survival of newborn cells in the hippocampus, a decrease in the number of these cells that differentiate into neurons and a diminished number of cells that are proliferating in the subgranular zone of the dentate gyrus. These results were further confirmed in vitro. Neurosphere cultures from adult mice deficient in C/EBP beta present less proliferation and neuronal differentiation than neurospheres derived from wild type mice. Conclusions/Significance: In summary, using in vivo and in vitro strategies, we have identified C/EBP beta as a key player in the proliferation and survival of the new neurons produced in the adult mouse hippocampus. Our results support a novel role of C/EBP beta in the processes of adult hippocampal neurogenesis, providing new insights into the mechanisms that control neurogenesis in this region of the brain.