Kandasamy, Mahesh and Lehner, Bernadette and Kraus, Sabrina and Sander, Paul Ramm and Marschallinger, Julia and Rivera, Francisco J. and Truembach, Dietrich and Ueberham, Uwe and Reitsamer, Herbert A. and Strauss, Olaf and Bogdahn, Ulrich and Couillard-Despres, Sebastien and Aigner, Ludwig (2014) TGF-beta signalling in the adult neurogenic niche promotes stem cell quiescence as well as generation of new neurons. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 18 (7). pp. 1444-1459. ISSN 1582-4934,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 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; TGF-1; Smad2; stem cells; cell cycle; doublecortin; differentiation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Oct 2019 13:24 |
| Last Modified: | 08 Oct 2019 13:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9920 |
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