Expression profiling has shown that the expression levels of many miRNAs is dynamically regulated during development,77,78 consistent with an emerging understanding for their important role in the development of brain structure and function.77,78 Dicer-deficient zebrafish, which lack all mature miRNAs, displayed marked defects in neural development.79,80 In Drosophila, dicer null mutation results in accumulation of pathogenic polyglutamine protein, a potent neurodegenerative agent.81 Further, deletion of miR-8 in flies can directly drive neurodegeneration.82 In mice, it was recently shown that miR-124 plays a critical role in differentiation of progenitor cells to mature neurons,83 similar to its role in zebrafish described above.80 Further, conditioned deletion of Dicer in Purkinje cells of mice resulted in cell-specific death of these cells, degradation of the cerebellum (within which Purkinje cells are located), and concomitant development of ataxia.84 These findings demonstrate that miRNAs play a central role in neuronal development and survival.
