Positional Specification in a Neural Stem Cell Line Involves Modulation of Musashi1 Expression

In this study, we have used an in vitro co-culture system to investigate the competency of a conditionally immortalized multipotential neural progenitor cell line (MHP36) to adopt "dorsal" or "striatal" telencephalic fates. We report that MHP36 cells, unlike primary fetal neural progenitors cells, do not express either dorsal or ventral telencephalic positional specification genes; at both the mRNA and protein levels, but that they quickly turn on expression of the appropriate set of proteins when cultured in either a dorsal (cortical) or a ventral (striatal) environment. This control has 2 components: transcriptional activation of positional specification genes, and translational control whereby only the appropriate set of mRNAs appears as immunoreactive protein. We show furthermore that this positional specification gene expression is modulated by the RNA-binding protein Musashi1. We postulate that it is the ability of MHP36 cells to adopt either cortical or striatal positional specification that is key to their functional efficacy in a number of models of neurological disease.