How to make a hippocampal dentate gyrus granule neuron

Granule neurons in the hippocampal dentate gyrus (DG) receive their primary inputs from the cortex and are known to be continuously generated throughout adult life. Ongoing integration of newborn neurons into the existing hippocampal neural circuitry provides enhanced neuroplasticity, which plays a crucial role in learning and memory; deficits in this process have been associated with cognitive decline under neuropathological conditions. In this Primer, we summarize the developmental principles that regulate the process of DG neurogenesis and discuss recent advances in harnessing these developmental cues to generate DG granule neurons from human pluripotent stem cells.