miRNAs in neurogenesis and brain tumor development
miRNAs function as important regulatory switches, influencing cell fate decisions and tumor development. miR-124, miR-128 and miR-137 are among the top-expressed miRNAs in the brain. They display parallel increase in expression as cells differentiate and their function is absolutely required for neuronal production. These three miRNAs are often repressed in glioblastoma and suggested to work as tumor suppressors. Our results indicate that miR-124, -128 and -137 act synergistically and control highly overlapping target sets. Interestingly, we also determined that miR-124, -128 and -137 share a large number of targets with Musashi1. In the antagonist model we propose to establish, Musashi1 and these three miRNAs have opposite impact on the expression of shared targets (activation by Musashi1 vs. repression by miR-124, -128 and -137). The concentration of each regulator would ultimately influence this network and neural stem cell fate with the options of self-renewal, differentiation or tumor development.