Divide or Commit – Revisiting the Role of Cell Cycle Regulators in Adult Hippocampal Neurogenesis

Abstract

The adult dentate gyrus continuously generates new neurons that endow the brain with increased plasticity, helping to cope with changing environmental and cognitive demands. The process leading to the birth of new neurons spans several precursor stages and is the result of a coordinated series of fate decisions, which are tightly controlled by extrinsic signals. Many of these signals act through modulation of cell cycle (CC) components, not only to drive proliferation, but also for linage commitment and differentiation. In this review, we provide a comprehensive overview on key CC components and regulators, with emphasis on G1 phase, and analyze their specific functions in precursor cells of the adult hippocampus. We explore their role for balancing quiescence versus self-renewal, which is essential to maintain a lifelong pool of neural stem cells while producing new neurons “on demand.” Finally, we discuss available evidence and controversies on the impact of CC/G1 length on proliferation versus differentiation decisions.