IMP2 regulates differentiation potentials of mouse neocortical neural precursor cells.

Neural precursor cells (NPCs) in the mammalian neocortex generate various neuronal and glial cell types in a developmental stage-dependent manner. Most neocortical NPCs lose their neurogenic potential after birth. We have previously shown that high-mobility group A (HMGA) proteins confer the neurogenic potential on early-stage NPCs during the midgestation period, although the underlying mechanisms are not fully understood. In this study, we found that HMGA2 promotes the expression of insulin-like growth factor 2 mRNA-binding protein 2 (IMP2, Igf2bp2) in neocortical NPCs. The level of IMP2 was indeed high in early-stage NPCs compared with that in late-stage NPCs. Importantly, over-expression of IMP2 increased the neurogenic potential and suppressed astrocytic differentiation of late-stage NPCs, whereas knockdown of IMP2 promoted astrocytic differentiation and reduced the neurogenic potential of early-stage neocortical NPCs without overtly affecting cell proliferation. Our results thus identified IMP2 as a developmental stage-dependent regulator of the differentiation potentials of NPCs in the mouse neocortex.