E-GEOD-57105 - Wip1 regulates adult neurogenesis and Wnt signaling during aging

Status
Released on 26 April 2014, last updated on 3 June 2014
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (12)
Description
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 Wnt pathway improved neuron formation and olfactory function in aged mice. We propose that Wip1 controls a Dkk3-dependent inhibition of neuronal differentiation during aging and thus regulating Wip1 levels could prevent certain aspects of functional decline of the aging brain. We found if neurospheres were derived from 18 months old mice, Wip1 transgenic neurospheres were more neurogenic than wt ones. This microarray was a pilot experiment to search the mechanism how Wip1 Transgene promoted neurogenesis, and found Dkk3 as a potential mediator. WT vs Wip1Tg neurospheres were cultured from mouse brain, and gene expression was compared using Illumina mouseWG-6 array
Experiment type
transcription profiling by array 
Contacts
Dmitry Bulavin, Yunhua Zhu
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-57105.idf.txt
Sample and data relationshipE-GEOD-57105.sdrf.txt
Processed data (1)E-GEOD-57105.processed.1.zip
Additional data (1)E-GEOD-57105.additional.1.zip
Array designA-MEXP-1175.adf.txt
Links