Wip1 regulates adult neurogenesis and Wnt signaling during aging

ABSTRACT: The number of newly-formed neurons declines rapidly during aging. Here we describe an important mechanism that contributes to this decline via Wip1-dependent regulation of neuronal differentiation. We found that Wip1 is expressed in neural stem/progenitor cells (NPCs) of the mouse subventricular zone and its upregulation at physiological levels maintained higher NPC numbers and neuronal differentiation in old mice. This resulted in markedly improved neuron formation and rescued a functional defect in fine odor discrimination in old mice. We identified Dkk3 as a key downstream target of Wip1 and found that its expression in SVZ is restricted to NPCs. Functionally, Dkk3 inhibited neuroblast formation by suppressing Wnt signaling, while deletion of Dkk3 or pharmacological reactivation of the

ORGANISM(S): Mus musculus

SUBMITTER: Dmitry Bulavin 

PROVIDER: E-GEOD-57105 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress