Engler, Anna Elisabeth. Notch signaling balances adult neural stem cell quiescence and heterogeneity. 2016, PhD Thesis, University of Basel, Faculty of Science.
Restricted to Repository staff only until 1 January 2018.
Official URL: http://edoc.unibas.ch/diss/DissB_12046
(1) What are the differences between active and quiescent NSCs?
(2) Do NSCs have similar maintenance factors in the SVZ and the SGZ?
(3) What are the capacities of distinct subtypes of NSCs and progenitors to respond to external stimuli?
I was able to show that in the adult mouse brain, Notch2 is the gatekeeper of quiescent NSCs in both neurogenic niches, the SVZ and the SGZ. The loss of this Notch paralogue led to the activation of quiescent NSCS and a prolonged and abnormal activation, followed by NSCs exhaustion in the long term. If Notch1 was deleted in addition to Notch2, quiescent and active NSCs are no longer maintained properly and will differentiate to a neural fate. Thus an intricate interplay between Notch1 and Notch2 is needed for adult NSC maintenance in both neurogenic niches.
In the SVZ the receptors Notch1 and Notch2 are coexpressed on NSCs. We addressed NSC identity also in the second neurogenic niche, the SGZ, where the receptors are also coexpressed by NSCs. The loss of Notch2 led to the activation of quiescent NSCs and an increased production of neuroblasts.
The differential signal requirement for the maintenance of quiescent and active NSCs raises the question, whether these distinct cell populations might have unique functions in response to external physiological and/or pathological stimuli. In order to address this question we characterized the SGZ in great detail at different ages. In the geriatric SGZ active NSCs were lost and the NSCs that remained were quiescent. These quiescent NSCs have the capacity to replenish the active NSC pool upon induction of epileptic seizures. On the other hand, administration of antidepressants left the NSCs unaffected initially. It was the amplifying progenitor pool that responded. In long-chase experiments the NSCs were then reactivated by either the resulting induced changes from the amplifying progenitors or a delay in NSC response.
NSC maintenance in the adult murine brain is an intricate mechanism highly dependent on the proper internal and external mechanisms. In the work presented here, I will illustrate the importance of Notch signaling in NSC maintenance and the high level of heterogeneity within the NSC pool and the NSC niche.
|Advisors:||Taylor, Verdon and Jessberger, Sebastian|
|Faculties and Departments:||03 Faculty of Medicine > Departement Biomedizin > Division of Anatomy > Embryology and Stem Cell Biology (Taylor)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||1 Online-Ressource (135 Seiten)|
|Last Modified:||03 Apr 2017 11:00|
|Deposited On:||03 Apr 2017 10:59|
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