NEPRO: a novel Notch effector for maintenance of neural progenitor cells in the neocortex

The Notch pathway is essential for maintaining neural progenitor cells (NPCs) in the developing brain. Activation of the pathway is sufficient to maintain NPCs, whereas loss-of-function mutations in the critical components of the pathway cause precocious neuronal differentiation and NPC depletion. Hairy and Enhancer of split (Hes)-type transcription factors have long been thought to be the only Notch effectors for the maintenance of NPCs. Recently, a novel nuclear protein, Nepro, has been identified as another critical effector of Notch. The Notch pathway is bifurcated into Nepro and Hes-type proteins in the early development of the neocortex. The combination of Nepro and Hes-type proteins is necessary and sufficient for maintaining NPCs downstream of Notch.