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Title: Characterisation of adult neural stem/progenitor cells in the murine hypothalamus
Author: Stewart, Iain
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2013
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Recent evidence has shown that adult neurogenesis is sustained in the hypothalamus, a region of the ventral diencephalon that is the central regulator of homeostasis. While studies support a role for adult neurogenesis in energy balance, as yet, the identity of the neural stem/progenitor cell niche remains contested. Tanycyte cells, a unique population to the hypothalamus, present a possible candidate due to their diverse roles, radial-glial like morphology and position adjacent to the 3rd ventricle. Here, I provide in-vivo, in-vitro and ex-vivo data that together support alpha-tanycytes as a neural stem/progenitor cell population. My studies show that the embryonic neural stem/progenitor characteristics of radial glia, including expression profile, a basal process and an apical primary cilium, are maintained in alpha-tanycytes during adulthood. In addition, alphatanycytes are multipotent in-vivo and contribute to the other tanycyte populations, suggesting a lineage relationship of cells within the hypothalamic ventricular zone. A neurosphere assay adds further validity to the idea that there is heterogeneity in progenitor status within tanycyte subpopulations. Furthermore, alpha-tanycytes are responsive to Fgf-signalling in-vivo, a crucial regulator of proliferation and differentiation during embryogenesis, as well as being required for neurosphere formation. In order to further interrogate alpha-tanycytes, I developed and optimised an organotypic slice culture protocol, a technique that has not yet been used to study hypothalamic neural stem/progenitor cell dynamics. This ex-vivo technique provides a number of advantages including efficiency, low-cost, and amenability to manipulation, while maintaining large parts of the niche. Exogenous addition of pharmacological agonists and inhibitors reveals that alpha-tanycytes undergo Fgf-dependent proliferation in response to physiological stimulation, and implicates a role for the hypothalamic niche in the homeostatic control of stress. Together, these studies characterise the component cells of the adult hypothalamic neural stem/progenitor cell niche, providing a framework for future research to further explore the heterogeneity and physiological significance of alpha-tanycytes.
Supervisor: Placzek, Marysia Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available