An Intrinsic Mechanism of Asymmetric Cell Division and Extrinsic Mechanism of Stem Cell Maintenance Underlies Adult Stem Cell Behaviour

The interplay between extrinsic and intrinsic processes as they influence a cell’s behaviour is a perennial question in both cellular and developmental biology. In this thesis these two issues are examined in the context of adult stem cells, a somatic stem cell present in the adult murine brain and a germline stem cell present in the adult Drosophila melanogaster ovary. I find that both of these distinct cell types exhibit patterns of non-random chromatid segregation in which the stem cells retain chromosomes carrying the older DNA strands. This unusual behaviour seems to exclusively occur in the context of differentiation, when one cell remains a stem cell and the other goes on to differentiate. Following these studies, the effects of extrinsic processes are tested in adult murine stem cells. It is determined that such cells can only produce neural progeny regardless of their association with foreign environments. These results argue against the phenomenon of stem cell plasticity which is proposed in several other systems and seem to support a primarily intrinsic-centered view of stem cell behaviour. However, the role of adhesion mediating proteins is next studied in such cells to determine their requirement for specific environments. The results of these experiments suggest that adult murine neural stem cells require association with support cells expressing E-Cadherin. Because the loss of such association results in a loss of stem cell number, these data show that intrinsic processes are insufficient to account for all stem cell behaviour. Indeed, based on these data and the results of other studies, it is hypothesized that the extrinsic association of stem cells in these diverse systems determines their polarity and subsequent intrinsic processes that enable these to divide asymmetrically. The implications of this theory are discussed with a view to general biological issues, the proximate mechanisms underlying these phenomena and the ultimate reasons these occur.Ph