Mitogen- and stress-activated kinases regulate progenitor cell proliferation and neuron development in the adult dentate gyrus

The neurogenic niche within the subgranular zone (SGZ) of the dentate gyrus is a source of new neurons throughout life. Interestingly, SGZ proliferative capacity is regulated by both physiological and pathophysiological conditions. One outstanding question involves the molecular mechanisms that regulate both basal and inducible adult neurogenesis. Here, we examined the role of the MAPK‐regulated kinases, mitogen‐ and stress‐activated kinase (MSK)1 and MSK2. as regulators of dentate gyrus SGZ progenitor cell proliferation and neurogenesis. Under basal conditions, MSK1/2 null mice exhibited significantly reduced progenitor cell proliferation capacity and a corollary reduction in the number of doublecortin (DCX)‐positive immature neurons. Strikingly, seizure‐induced progenitor proliferation was totally blocked in MSK1/2 null mice. This blunting of cell proliferation in MSK1/2 null mice was partially reversed by forskolin infusion, indicating that the inducible proliferative capacity of the progenitor cell population was intact. Furthermore, in MSK1/2 null mice, DCX‐positive immature neurons exhibited reduced neurite arborization. Together, these data reveal a critical role for MSK1/2 as regulators of both basal and activity‐dependent progenitor cell proliferation and morphological maturation in the SGZ. Throughout life, the subgranular zone (SGZ) neurogenic niche seeds the dentate gyrus with new neurons. In this study we examined the role of the ERK/MAPK effectors mitogen‐stress activated kinases 1 and 2 (MSK1/2) in SGZ progenitor cell proliferation and neuron morphological maturation. The data presented here indicate that MSK1/2 play key roles in regulating basal and inducible SGZ progenitor proliferation as well as regulating the morphological maturation of adult‐born neurons.