Abstract
The mechanisms involved in regulation of quiescence, proliferation, and reprogramming of Neural Stem Progenitor Cells (NSPCs) of the mammalian brain are still poorly defined. Here, we studied the role of the transcriptional co-factor TAZ, regulated by the WNT and Hippo pathways, in the homeostasis of NSPCs. We found that, in the murine neurogenic niches of the striatal subventricular zone and the dentate gyrus granular zone, TAZ is highly expressed in NSPCs and declines with ageing. Moreover, TAZ expression is lost in immature neurons of both neurogenic regions. To characterize mechanistically the role of TAZ in neuronal differentiation, we used the midbrain-derived NSPC line ReNcell VM to replicate in a non-animal model the factors influencing NSPC differentiation to the neuronal lineage. TAZ knock-down and forced expression in NSPCs led to increased and reduced neuronal differentiation, respectively. TEADs-knockdown indicated that these TAZ co-partners are required for the suppression of NSPCs commitment to neuronal differentiation. Genetic manipulation of the TAZ/TEAD system showed its participation in transcriptional repression of SOX2 and the proneuronal genes ASCL1, NEUROG2, and NEUROD1, leading to impediment of neurogenesis. TAZ is usually considered a transcriptional co-activator promoting stem cell proliferation, but our study indicates an additional function as a repressor of neuronal differentiation.
Highlights
In mammals, a subpopulation of embryonic neural precursors persists into adulthood as neural stem progenitor cells (NSPCs) and localizes at neurogenic niches, such as the subventricular zone (SVZ) of the striatum and the subgranular zone (SGZ) of the hippocampus
The regulatory networks that control the dynamics of Neural Stem Progenitor Cells (NSPCs) in the SVZ and the SGZ are a subject of high interest in order to understand
Genetic programs aimed at maintenance of stemness vs. commitment to differentiation into specific cellular lineages are tightly governed by epigenetic modifications and remodeling of chromatin
Summary
A subpopulation of embryonic neural precursors persists into adulthood as neural stem progenitor cells (NSPCs) and localizes at neurogenic niches, such as the subventricular zone (SVZ) of the striatum and the subgranular zone (SGZ) of the hippocampus. Despite some controversy in human studies [1], the general view is that NSPCs provide a source of neurons that may be relevant for the maintenance of brain functions, including cognition [2,3] and motor functions [4,5]. The regulatory networks that control the dynamics of NSPCs in the SVZ and the SGZ are a subject of high interest in order to understand. Cells 2020, 9, 2230 their participation in brain pathophysiology. These networks include the WNT and the Hippo signaling pathways which converge at the regulation of neural stem cells fate [6]. Transcriptional co-activators TAZ (transcriptional coactivator with PDZ binding motif) and YAP
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
