AbstractsBiology & Animal Science

The embryonic and adult central nervous systems (CNS) harbor heterogeneous populations of proliferating neural progenitor cells which are capable of generating both neurons and glia in vivo and in vitro. These populations serve to generate all neural cell types throughout development as well as maintain neural cell populations during periods of cellular turnover or injury. However, the cellular and molecular mechanisms which regulate the cell-fate decisions of these distinct progenitor populations are unclear. Moreover, the ability to identify neural progenitor populations in vivo is hindered by a lack of defined molecular markers which are capable of specifically recognizing these cells. Thus additional tools are necessary for the continued analysis of neural progenitors in vivo. The HMG-BOX transcription factor SOX2 is expressed in a majority of spatially and temporally distinct neural progenitor populations within the developing and adult CNS. SOX2 has been demonstrated to maintain the proliferative and differentiation capacity of neural progenitor cells in the spinal cord and retina and is important for proper neuronal differentiation and cortical development in mice. However, SOX2 has not been fully characterized in molecularly distinct neural progenitor populations in the CNS nor has its function been addressed in neural progenitor cells that appear during later stages of neural development. In this dissertation I generate and characterize the SOX2EGFP mouse line which allows for the prospective identification of SOX2-positive neural progenitor cells in the developing and adult CNS in vivo. I next demonstrate that distinct populations of neural progenitor cells can be prospectively isolated from the CNS based upon their intracellular concentrations of SOX2. Lastly, I demonstrate that SOX2 function is necessary for the proper maintenance of radial glial cells in the dorsal telencephalon as loss of SOX2 results in a decrease in the number of proliferating radial glia and intermediate progenitors, as well as a reduction in their self-renewal capacity. Collectively these results demonstrate that SOX2 (via the SOX2EGFP mouse line) can efficiently identify neural progenitor populations within the CNS and, more importantly, that SOX2 function is critical for the proper maintenance of neural progenitor populations in the developing CNS.