Role of C/EBPβ Transcription Factor in Adult Hippocampal Neurogenesis

Abstract

BackgroundThe 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 β (C/EBPβ) is expressed in the granular layer of the dentate gyrus of the adult mouse hippocampus. Taking into account the important role of C/EBPβ 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 FindingsHere, we show, using C/EBPβ knockout mice, that C/EBPβ expression is observed in the subset of newborn cells that proliferate in the hippocampus of the adult brain. Mice lacking C/EBPβ 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/EBPβ present less proliferation and neuronal differentiation than neurospheres derived from wild type mice.Conclusions/SignificanceIn summary, using in vivo and in vitro strategies, we have identified C/EBPβ 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/EBPβ in the processes of adult hippocampal neurogenesis, providing new insights into the mechanisms that control neurogenesis in this region of the brain.

C/EBPβ and C/EBPδ transcription factors: Basic biology and roles in the CNS

“…This suggests a role for C/EBPβ promoting neurogenesis which is supported by the upregulation of C/EBPβ in neuronal A c c e p t e d M a n u s c r i p t 47 differentiation in human neural stem cells in vitro (Cheeran et al 2005) and in murine neural progenitor cells in the subventricular zone in vivo ). In agreement with this, C/EBPβ deficient mice show reduced neurogenesis in vitro and in vivo (Cortes-Canteli et al 2011). Therefore, with the exception of one study reporting that C/EBPβ inhibition is associated with TNFα-induced neuronal differentiation of neural stem cells (Zhang et al 2012a), most experimental data support a role for C/EBPβ in promoting neurogenesis.…”

Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression

“…The C/EBP family is comprised of basic leucine zipper transcription factors that participate in multiple process of tissue homeostasis through regulation of cell proliferation and differentiation5354. C/EBPβ is thought to be particularly important for neural stem cell maintenance and neural regeneration565758. Cortes-Cantei et al ., showed that C/EBPβ plays a critical role in neurogenesis in the adult hippocampus, where it is expressed in the newly generated neural stem cells of the dentate gyrus (DG).…”

“…Cortes-Cantei et al ., showed that C/EBPβ plays a critical role in neurogenesis in the adult hippocampus, where it is expressed in the newly generated neural stem cells of the dentate gyrus (DG). Loss of C/EBPβ results in reduced cell proliferation and impaired differentiation of newly generated neurons in the adult hippocampal DG in vivo 57. Zhang et al .…”

LncRNA Riken‐201 and Riken‐203 modulates neural development by regulating the Sox6 through sequestering miRNAs

“…43 By performing a double luciferase assay, the transcription factor 43 By performing a double luciferase assay, the transcription factor …”

“…Sox6 restored the mESC neural differentiation to NPCs repressed by knockdown of the Rik-201 and Rik-203. Mice lacking C/EBPβ 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 proliferate in the subgranular zone of the dentate gyrus 43. However, there are currently no studies that show the potential impact of miRNA/Sox6 regulatory pathway on the neural development-related process.…”