Oscillatory control of bHLH factors in neural progenitors

• The expression of multiple basic helix-loop-helix (bHLH) factors oscillates in multipotent neural progenitors.
• The expression of a selected bHLH factor becomes sustained during fate determination.
• Ascl1 exhibits opposing functions depending on the expression dynamics.
• The bHLH factor oscillations form a hierarchy with Hes1 holding the highest position.

The mammalian brain consists of a complex ensemble of neurons and glia. Their production during development and remodeling is tightly controlled by various regulatory mechanisms in neural progenitor cells (NPCs). Among such regulations, basic helix-loop-helix (bHLH) factors have key functions in the self-renewal, multipotency, and fate determination of NPCs. Here, we highlight the importance of the expression dynamics of bHLH factors in these processes. The oscillatory expression of multiple bHLH factors is correlated with the multipotent and self-renewable state, whereas sustained expression of a selected bHLH factor regulates fate determination. We also discuss potential mechanisms by which a single bHLH factor can exhibit versatile functions in NPC regulation as well as the hierarchical structure of the bHLH factor oscillatory network.