Controlling neural stem and progenitor cell (NSPC) proliferation is critical to maintain neurogenesis in the mammalian brain throughout life. However, it remains poorly understood how niche-derived cues such as β1-integrin-mediated signaling are translated into NSPC-intrinsic molecular changes to regulate NSPC activity. Here we show that genetic deletion of integrin-linked kinase (ILK) increases NSPC proliferation through PINCH1/2-dependent enhancement of c-Jun N-terminal protein kinase activity in both neurogenic regions of the adult mouse brain. This effect downstream of ILK signaling is mediated through loss of Ras suppressor unit-1 (RSU-1), as virus-based reconstitution of RSU-1 expression rescued the ILK-dependent effects on NSPC proliferation. Thus, we here identified an intracellular signaling cascade linking extrinsic integrin-mediated signaling to NSPC proliferation and characterized a novel mechanism that regulates NSPC activity in the adult mammalian brain.
Keywords: hippocampus; integrin; neurogenesis; niche; proliferation.