Gene regulatory networks controlling neuronal development: enhancers, epigenetics, and functional RNA

Abstract Gene regulation underlies the diversity in form and function of cell types in the brain. Here, we summarize the basic principles of gene regulatory networks that produce the dynamic expression patterns that distinguish neuronal cell types. We discuss the interplay between regulatory DNA, epigenetics, and relevant proteins and functional RNAs that determine transcriptional output. We present a perspective describing how gene regulatory networks are established that goes from early work defining major transcription factors controlling such networks to recent efforts to understand how such networks function at the molecular and genomic level. Finally, we provide examples of efforts to define the regulatory networks that drive neuronal differentiation and review emerging evidence for a critical role for mutations that perturb such regulatory networks in neurodevelopmental and neuropsychiatric disorders.