edoc

RBPJkappa-dependent signaling is essential for long-term maintenance of neural stem cells in the adult hippocampus

Ehm, O. and Goritz, C. and Covic, M. and Schaffner, I. and Schwarz, T. J. and Karaca, E. and Kempkes, B. and Kremmer, E. and Pfrieger, F. W. and Espinosa, L. and Bigas, A. and Giachino, C. and Taylor, V. and Frisen, J. and Lie, D. C.. (2010) RBPJkappa-dependent signaling is essential for long-term maintenance of neural stem cells in the adult hippocampus. Journal of Neuroscience, 30 (41). pp. 13794-13807.

[img]
Preview
PDF - Published Version
Available under License CC BY (Attribution).

4Mb

Official URL: http://edoc.unibas.ch/dok/A6338052

Downloads: Statistics Overview

Abstract

The generation of new neurons from neural stem cells in the adult hippocampal dentate gyrus contributes to learning and mood regulation. To sustain hippocampal neurogenesis throughout life, maintenance of the neural stem cell pool has to be tightly controlled. We found that the Notch/RBPJkappa-signaling pathway is highly active in neural stem cells of the adult mouse hippocampus. Conditional inactivation of RBPJkappa in neural stem cells in vivo resulted in increased neuronal differentiation of neural stem cells in the adult hippocampus at an early time point and depletion of the Sox2-positive neural stem cell pool and suppression of hippocampal neurogenesis at a later time point. Moreover, RBPJkappa-deficient neural stem cells displayed impaired self-renewal in vitro and loss of expression of the transcription factor Sox2. Interestingly, we found that Notch signaling increases Sox2 promoter activity and Sox2 expression in adult neural stem cells. In addition, activated Notch and RBPJkappa were highly enriched on the Sox2 promoter in adult hippocampal neural stem cells, thus identifying Sox2 as a direct target of Notch/RBPJkappa signaling. Finally, we found that overexpression of Sox2 can rescue the self-renewal defect in RBPJkappa-deficient neural stem cells. These results identify RBPJkappa-dependent pathways as essential regulators of adult neural stem cell maintenance and suggest that the actions of RBPJkappa are, at least in part, mediated by control of Sox2 expression.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Anatomy > Embryology and Stem Cell Biology (Taylor)
UniBasel Contributors:Taylor, Verdon
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Society for Neuroscience
ISSN:0270-6474
e-ISSN:1529-2401
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
edoc DOI:
Last Modified:27 Nov 2017 14:37
Deposited On:10 Apr 2015 09:13

Repository Staff Only: item control page