Open AccessTGF‐beta signalling in the adult neurogenic niche promotes stem cell quiescence as well as generation of new neurons
Author(s) -
Kandasamy Mahesh,
Lehner Bernadette,
Kraus Sabrina,
Sander Paul Ramm,
Marschallinger Julia,
Rivera Francisco J.,
Trümbach Dietrich,
Ueberham Uwe,
Reitsamer Herbert A.,
Strauss Olaf,
Bogdahn Ulrich,
CouillardDespres Sebastien,
Aigner Ludwig
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12298
Subject(s) - biology , neural stem cell , stem cell , microbiology and biotechnology , progenitor cell , adult stem cell , cellular differentiation , neuroscience , genetics , gene
Members of the transforming growth factor ( TGF )‐β 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 ‐β 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 ‐β1 signalling in the hippocampal neural stem cell niche of a transgenic mouse that was previously generated to express TGF ‐β1 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 ‐β1 in vitro and in vivo conditions. Finally, we performed a gene expression profiling to identify the targets of TGF ‐β1 signalling in adult NPC s. The results demonstrate that TGF ‐β1 promotes stem cell quiescence on one side, but also neuronal survival on the other side. Thus, considering the elevated levels of TGF ‐β1 in ageing and neurodegenerative diseases, TGF ‐β1 signalling presents a molecular target for future interventions in such conditions.