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Kandasamy, M.* ; Lehner, B.* ; Kraus, S.* ; Sander, P.R.* ; Marschallinger, J.* ; Rivera, F.J.* ; Trümbach, D. ; Ueberham, U.* ; Reitsamer, H.A.* ; Strauss, O.* ; Bogdahn, U.* ; Couillard-Despres, S.* ; Aigner, L.*

TGF-beta signalling in the adult neurogenic niche promotes stem cell quiescence as well as generation of new neurons.

J. Cell. Mol. Med. 18, 1444-1459 (2014)
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Members of the transforming growth factor (TGF)- family govern a wide range of mechanisms in brain development and in the adult, in particular neuronal/glial differentiation and survival, but also cell cycle regulation and neural stem cell maintenance. This clearly created some discrepancies in the field with some studies favouring neuronal differentiation/survival of progenitors and others favouring cell cycle exit and neural stem cell quiescence/maintenance. Here, we provide a unifying hypothesis claiming that through its regulation of neural progenitor cell (NPC) proliferation, TGF- signalling might be responsible for (i) maintaining stem cells in a quiescent stage, and (ii) promoting survival of newly generated neurons and their functional differentiation. Therefore, we performed a detailed histological analysis of TGF-1 signalling in the hippocampal neural stem cell niche of a transgenic mouse that was previously generated to express TGF-1 under a tetracycline regulatable Ca-Calmodulin kinase promoter. We also analysed NPC proliferation, quiescence, neuronal survival and differentiation in relation to elevated levels of TGF-1 in vitro and in vivo conditions. Finally, we performed a gene expression profiling to identify the targets of TGF-1 signalling in adult NPCs. The results demonstrate that TGF-1 promotes stem cell quiescence on one side, but also neuronal survival on the other side. Thus, considering the elevated levels of TGF-1 in ageing and neurodegenerative diseases, TGF-1 signalling presents a molecular target for future interventions in such conditions.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Tgf-1 ; Smad2 ; Stem Cells ; Cell Cycle ; Doublecortin ; Differentiation; Growth-factor-beta; Central-nervous-system; Neural Progenitor Cells; Transforming Growth-factor-beta-1; Transgenic Mice; Hippocampal Neurogenesis; Subventricular Zone; Alzheimers-disease; Mouse-brain; Tgf-beta-1
Language english
Publication Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 1582-1838
e-ISSN 1582-4934
Journal Journal of Cellular and Molecular Medicine
Quellenangaben Volume: 18, Issue: 7, Pages: 1444-1459 Article Number: , Supplement: ,
Publisher Blackwell
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500500-001
PubMed ID 24779367
DOI 10.1111/jcmm.12298
WOS ID WOS:000340413500019
Erfassungsdatum 2014-09-15
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