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Elucidating the role of NrCAM in the hypothalamic stem cell niche

Moore, Alexander W (2018) Elucidating the role of NrCAM in the hypothalamic stem cell niche. PhD thesis, University of Sheffield.

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Abstract

Hypothalamic tanycytes are highly specialised glia that interface with the fenestrated capillaries of the median eminence, hypothalamic neurons, and the cerebrospinal fluid of the 3rd ventricle, serving a vital role in the regulation of homeostatic control. Stereotypically, tanycytes are divided into four subsets which express an array of different markers. Recent studies show that tanycytes in adult mice include a subset of neurogenic stem/progenitor cells, though reports conflict when identifying which subset is neurogenic. Furthermore, most reports focus on tanycytes in the medial hypothalamus, but do not discuss how their findings relate to tanycytes of anterior and posterior hypothalamic subregions. In this study I characterise a variety of established tanycyte markers across the anterior-posterior axis of the hypothalamus, describe the cell adhesion molecule NrCAM as a new tanycyte marker, and show, for the first time, Sonic Hedgehog (Shh) expression in a tanycyte subset around the adult mouse 3rd ventricle. My results show that classic tanycyte subsets vary in dorso-ventral localisation across the anterior-posterior (A-P) hypothalamic axis, and suggest a new 3D model for tanycyte location that could improve on our understanding of tanycyte subset function. Based on the localisation of fibroblast growth factor 10 (Fgf10) and Shh in the adult posterior median eminence, I propose this region be further investigated as the site of a potential hypothalamic stem cell population. I addition, I have begun to investigate the role of NrCAM by studying the hypothalamic phenotype in adult and embryonic mice lacking NrCAM. I show that loss of NrCAM induces a reduction of tanycytes and their embryonic radial-glial precursors. This is complemented by a decrease in hypothalamic dopaminergic neurons in adult mice, and an increase in the embryo. Together my work suggests a role for NrCAM in the development and/or maintenance of hypothalamic tanycytes and neuronal populations.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > Biomedical Science (Sheffield)
Depositing User: Dr Alexander W Moore
Date Deposited: 25 Mar 2019 10:13
Last Modified: 25 Mar 2019 10:13
URI: http://etheses.whiterose.ac.uk/id/eprint/23383

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