eprintid: 10097941
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/09/79/41
datestamp: 2020-08-20 14:27:18
lastmod: 2020-08-20 14:27:18
status_changed: 2020-08-20 14:27:18
type: thesis
metadata_visibility: show
creators_name: Ortiz-Sanchez, Marco Antonio
title: Role of Sonic Hedgehog signalling in regulating neural stem cell activity in the adult and aged murine hippocampus
ispublished: unpub
divisions: UCL
divisions: A01
divisions: B02
divisions: C08
note: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Licence (https://creativecommons.org/licenses/by-nc-nd/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
abstract: The homeostatic behaviour of neural stem cells (NSCs) in the adult hippocampus is controlled by signals from the niche. In young mice, the activation of dormant NSCs is typically followed by consecutive divisions producing neuronal progenitors followed by astrocyte differentiation, resulting in a rapid depletion of the NSC population. In a subset of active NSCs, however, the proactivation factor ASCL1 is degraded by the ubiquitinligase HUWE1, resulting in the return of these NSCs to a transient state of quiescence. These resting NSCs show a high propensity to reactivate and are essential for the maintenance of neurogenesis. How niche signals control the generation of the different NSC populations in appropriate ratios to ensure the long-term maintenance of neurogenesis is unknown. In my thesis, I have studied the regulation of NSC activity in the adult and mature mouse hippocampus by Sonic hedgehog (Shh) signalling. Firstly, I show that NSCs are able to respond to Shh signalling and that in young mice, this promotes activation of dormant NSCs and suppresses the formation of resting NSCs by inhibiting HUWE1-mediated degradation of ASCL1. In older mice, however, I show that Shh signalling activity diminishes progressively, which slows down the rate of NSC depletion. Finally, I identify oligodendrocyte cells as a cellular source of Shh in the adult hippocampus. My results provide cellular and molecular insights into the preservation of the hippocampal NSC pool in mature mice.
date: 2020-05-28
date_type: published
oa_status: green
full_text_type: other
thesis_class: doctoral_open
thesis_award: Ph.D
language: eng
thesis_view: UCL_Thesis
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1782783
lyricists_name: Ortiz Sanchez, Marco
lyricists_id: MAORT15
actors_name: Ortiz Sanchez, Marco
actors_name: Austen, Jennifer
actors_id: MAORT15
actors_id: JAUST66
actors_role: owner
actors_role: impersonator
full_text_status: public
pages: 212
event_title: UCL (University College London)
institution: UCL (University College London)
department: Division of Biosciences
thesis_type: Doctoral
citation:        Ortiz-Sanchez, Marco Antonio;      (2020)    Role of Sonic Hedgehog signalling in regulating neural stem cell activity in the adult and aged murine hippocampus.                   Doctoral thesis  (Ph.D), UCL (University College London).     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10097941/1/Ortiz%20Sanchez_000_thesis.pdf