Neural Stem / Progenitor Cells in the Adult Mouse Hypothalamus

Adult neural stem cells are now widely accepted to exist in the neurogenic regions of the subventricular zone and dentate gyrus; however there is increasing evidence to suggest that neurogenesis may also occur in other brain regions. It has been proposed that one such population of neural stem cells resides in the hypothalamus, more specifically in the ependymal lining of the third ventricle. In this thesis, I tested the hypothesis that stem cells exist in defined regions of the adult mouse hypothalamus. My work confirms the presence of stem / progenitor cells in the adult mouse hypothalamus. Analysis of neural ‘stem cell markers,’ both in vivo and in vitro, suggests the presence of different populations of stem / progenitor cells occupying discrete territories of the ependymal zone. Some markers are common to those found in other adult neural stem cell niches, whilst others are unique to the hypothalamus. I have isolated hypothalamic stem / progenitor cells, and assayed their character and potential for both self-renewal and differentiation using the neurosphere assay. I show that hypothalamic neurospheres can be propagated in culture for extended periods of time, and that they can differentiate into cells of all three neural lineages. I have also determined the precise location of neurosphere-forming cells in the hypothalamus, showing that proliferative capacity is restricted to defined regions. Within these regions, I have also identified separate populations of proliferating cells that vary in their capacity for self-renewal, and correlated this with marker profiles. This data supports previous reports suggesting that tanycytes act as neural stem cells in the hypothalamus. Finally, I have started work investigating the control of hypothalamic stem / progenitor proliferation by fibroblast growth factors. I demonstrate that FGF signalling is necessary for in vitro proliferation. Finally, my studies suggest that endogenous FGFs may regulate hypothalamic stem cell proliferation.