Epigenetic Regulation of Neurogenesis by microRNAs

The specification of multipotent stem cells to defined cell types requires complex integrations of genetic pathways. During neurogenesis-the process of generating functional neurons from neural progenitor cells (NPCs)-many epigenetic processes play a critical role in regulating genes that control the proliferation and differentiation of NPCs. MicroRNAs (miRNAs) play an important role upstream of neurodevelopmental processes through chromatin regulation. During neural development, miRNAs, particularly brain-enriched miR-9/9* and miR-124, modulate neurogenesis by targeting many key epigenetic pathways that affect the transcriptional accessibility of chromatin regions as well as mRNA processing. Importantly, ectopic expression of miR-9/9* and miR-124 in human fibroblasts induces the cells to adopt a neuronal fate. Direct conversion of a nonneuronal somatic cell to a functional neuron by brain-enriched miRNAs not only emphasizes the essential role of miRNAs in neurogenesis, but also provides new strategies for modeling human neurodegenerative diseases and regenerative medicine.