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Title: Progenitor populations within the vertebrate enteric nervous system
Author: McCallum, Sarah
ISNI:       0000 0004 7964 8837
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Tissue maintenance and repair depends on specialised cell types with the capacity to replenish cellular compartments lost by normal turnover or disease. Within the enteric nervous system (ENS), enteric glial cells (EGCs) play roles in: supporting enteric neurons, modulating inflammation, enhancing epithelial barrier fitness and, under certain experimental conditions, regenerating the ENS. Nevertheless, the cellular and molecular basis of the regenerative capacity and the extent of regeneration of the ENS is unknown. We use zebrafish, a model organism particularly amenable to genetic, developmental and functional studies, to study the organisation and function of EGCs, including their potential role in ENS maintenance and regeneration. Since limited studies have examined EGCs in zebrafish, we first combined transgenic reporter analysis with immunostaining to characterise the EGC population in zebrafish. Our experiments led to the identification of a population of EGCs within the ENS that are closely associated with enteric neurons and express the neural crest marker Sox10, but surprisingly lack canonical peripheral glial markers. However, these cells express the Notch effector bHLH transcription factor Her4.1, and have characteristic ultrastructural features of EGCs. Since, Her4.1 is an established marker of radial glia in the zebrafish CNS, a known progenitor cell type we used EdU chase experiments and mathematical modelling to reveal the proliferative and neurogenic potential of Her4.1 cells in the adult zebrafish ENS. Moreover, we employed Notch inhibitors to show that Notch signalling promotes EGC quiescence and maintenance of the non-neuronal cell fate. Finally, using transgenic lines we identified expression of HES5, the mammalian orthologue of Her4.1, within a subpopulation of Type I mammalian EGCs, identifying the first subtype marker of mammalian EGCs. This work provides the first characterisation of zebrafish EGCs, and identifies a novel marker of EGCs in both the zebrafish and mouse ENS with putative stem cell properties.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available