Control of oligodendroglial cell number by the miR-17~92 family of miRNA cluster (miRNA Exiqon Part)

The generation of myelinating cells in the central nervous system (CNS) requires the initiation of specific gene-expression programs in oligodendrocytes. We reasoned that miRNAs could play an important role in this process by regulating critical developmental genes. Microarray profiling of cultured oligodendrocytes identifies the miR-17~92 family of miRNA cluster as highly enriched miRNAs in oligodendrocytes.We specifically deleted the miR-17~92 cluster in oligodendrocytes using the 2´3´-cyclic nucleotide 3´-phosphodiesterase (CNP)-Cre mice. Absence of miR-17~92 leads to a reduction of oligodendrocyte number in vivo and we find that the expression of these miRNAs in primary cultures of oligodendrocytes promotes cell proliferation by influencing Akt signalling. Together, these results suggest that the miRNA pathway is essential in determining oligodendroglial cell number and that the miR-17~92 cluster is crucial in this process. miRNA microarray profiling was used for the identification of miRNAs enriched in oligodendrocytes. Total RNA lysates from primary oligodendroctes compared to primary astrocytes were analysed regarding their miRNA levels. Three independent samples for each of the two cell types were used. The study was initially designed with a comparison of oligodendrocytes, astrocytes and microglia. However, only the comparison of oligodendrocytes and astrocytes is discussed in the present study.