Since the discovery of short, regulatory microRNAs (miRNA) 20 years ago, the understanding of their impact on gene regulation has dramatically increased. Differentiation of cells requires comprehensive changes in regulatory networks at all levels of gene expression. Posttranscriptional regulation by miRNA leads to rapid modifications in the protein level of large gene networks, and it is therefore not surprising that miRNAs have been found to influence the fate of differentiating cells. Several recent studies have shown that overexpression of a single miRNA in different cellular contexts results in forced differentiation of nerve cells. Loss of this miRNA constrains neurogenesis and promotes gliogenesis. This miRNA, miR-124, is probably the most well-documented example of a miRNA that controls nerve cell fate determination. In this review we summarize the recent findings on miR-124, potential molecular mechanisms used by miR-124 to drive neuronal differentiation, and outline future directions.
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