Stage-dependent fate determination of neural precursor cells in mouse forebrain.

Cortical neural precursor cells (NPCs) sequentially undergo expansion, neurogenic and gliogenic phases during development, although the underlying mechanisms are poorly understood. Recent studies have identified a number of extrinsic factors that regulate the fate of NPCs. For example, we have shown that Wnt signaling induces neuronal differentiation of NPCs in an instructive manner. Importantly, Wnt signaling does so in late stage (neurogenic phase) of NPCs but not in early stage (expansion phase) of NPCs. Instead, Wnt signaling promotes proliferation of early NPCs. Likewise, STAT3-activating ligands induce astrocytic differentiation in late (gliogenic phase) but not in early (expansion and neurogenic phases) NPCs. These stage-dependent responses of NPCs might play a central role in determining the timing of differentiation and the size of final population of each differentiated cell type.