Another powerful tool that improved our understanding of the functional relevance of miRNAs in neuronal tissues was the development of mice with genetic manipulations in the genes encoding Dicer and Arognaute2 (Ago2). Both of these proteins are important components of the miRNA biogenesis pathway. Dicer is an endoribonuclease that catalyzes the processing of precursor miRNA into its mature form. Characterization of Dicer1 mutants in C. elegans suggested that this protein plays a critical role in brain development (Grishok et al., 2001). To assess its role in mammalian brain development Bernstein et al. disrupted Dicer in mice and observed embryonic lethality with depleted number of stem cells, suggesting that this enzyme is important for development in general (Bernstein et al., 2003). Subsequently a number of groups knocked down Dicer via conditional gene targeting, with the findings consistent in demonstrating that ablation of dicer results in decreased miRNA expression and defects in neuronal cell differentiation and survival (Kanellopoulou et al., 2005; Murchison et al., 2005; Schaefer et al., 2007). These phenotypes could be rescued by re-expression of the gene (Kanellopoulou et al.,
