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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)
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
ISSN (print) / ISBN
1582-1838
e-ISSN
1582-4934
Quellenangaben
Volume: 18,
Issue: 7,
Pages: 1444-1459
Publisher
Blackwell
Publishing Place
Hoboken
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)