MicroRNAs are small, non-coding RNAs that regulate expression of their target genes by controlling transcription and/or translation. Thus, microRNAs provide a new mode of regulation of cell differentiation. In previous studies, we observed that forced expression of the early neural inducer noggin promoted proliferation and neuronal differentiation of subventricular zone (SVZ) neural progenitors and also inhibited expression of a novel microRNA-410 (miR-410). Therefore, I hypothesized that miRNA-410 may play a role in controlling self-renewal or neurogenesis in the adult mouse brain. Expression of miR-410 is restricted to the CNS in E11.5 mouse embryos; later it is expressed in the rhombic lip of the fourth ventricle and SVZ. To test its role in neural stem cells, neurospheres derived from the adult SVZ were transfected with a miR-410 expression vector, a miRNA sponge vector to knock down miR-410, or control constructs. Differentiation of the neurospheres into neurons (Tuj1+), glia (GFAP+), and oligodendrocytes (MBP+) was quantified using both immunohistochemistry and q-RT-PCR. The number of Tuj1 positive neurons was increased by miR-410 knock-down and decreased by the over-expression of miR-410. Meanwhile, the number of GFAP positive astrocytes was significantly decreased in miR-410 sponge transfected cells, compared with controls. miR-410 over-expression rescued the increase in Tuj1 positive neurons and the decrease in GFAP positive astrocytes caused by Noggin. In additional studies, two mouse ES cell lines over-expressing miR-410 were generated from the D3 ES cell line. After 5 days of hanging drop culture, the diameters of embryoid bodies (EBs) formed from each cell line were compared. Over-expression of miR-410 significantly reduced the size of the EBs, compared with parental cell line. When differentiated in monolayer in defined neural medium, there was widespread differentiation of Sox3 positive neural precursors and Tuj1 positive neurons. However in both miR-410 over-expressing cell lines neural (Sox3+) and neuronal (Tuj1+) differentiation was strikingly inhibited. Consistent with these results, computer predicted targets of miR-410 identified genes involved in neuronal differentiation including ELAV, Msi2 and Tcf4. Overall, these results support the conclusion that miR-410 controls self-renewal and lineage differentiation of neural stem cells.