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

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 npcs. 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. © 2014 the authors.