Transcriptional Regulation of Adult Neurogenesis by NRSF/REST and NeuroD1

Neurogenesis in the adult brain is a complex and lifelong process that is regulated by multiple pathways and is sensitive to many external stimuli. Two critical regulatory factors in this process are NRSF/REST and NeuroD1. NRSF/REST, a transcriptional repressor that binds a specific NRSE site and recruits corepressors and chromatin remodeling machinery to repress its target genes, is critical for maintenance of the neural stem cell pool and for proper pacing of neuronal differentiation. NeuroD1, a bHLH transcription factor, is necessary for the terminal differentiation, maturation, and survival of newborn neurons. In addition, both factors are necessary for the neurogenic response to both physiological and pathological stimuli, which may induce neurogenesis through different pathways. Thus, NRSF/REST and NeuroD1 are necessary for neurogenesis to occur correctly, to persist throughout the organism’s lifespan, and to respond to external stimuli.