Notch controls proliferation and differentiation of stem cells in a dose-dependent manner

Self-renewal and differentiation of CNS stem cells are regulated by still poorly understood cell-cell interactions. Notch is a well-known cell surface protein that can promote both cell cycle progression and mitotic arrest but the molecular mechanism controlling these opposite effects is unknown. Here we demonstrate that, in CNS stem cells, the level of active Notch1 determines the cellular response. Specifically, low levels of the active form of Notch1 promote proliferation whereas high levels lead to growth arrest. Here we provide the first evidence that Notch effects on proliferation and differentiation are a function of dose, and propose a hypothesis on how oncogenes may also act as tumor suppressors.