We are interested in investigating the classical support roles of the radial glia (RG) cell population. This transitory cell type, that has recently been shown to include a class of multipotent progenitors, plays many pivotal roles during development. However, many of the well accepted support functions of RG, such as acting as guides for neuronal migration and axonal elongation, trophic support, establishment of boundaries and compartments have not been directly and fully investigated. One direct approach, the specific ablation of this class of cells and analysis of the resultant phenotype, has not been successfully achieved to date. We will employ an in vivo approach of targeted photolytic degeneration to eliminate the radial glial population of the postnatal cerebral cortex. This approach is based on the retrograde transport of nanospheres carrying a chromophore (chlorin e6) that once photoactivated produces cytotoxic singlet oxygen molecules that lead to the apoptotic death of the labeled cells. We have chosen the postnatal cerebral cortex because, at this stage, RG are likely to serve primarily support functions. Postnatally RG shows little if any proliferative activity. By eliminating RG in spatially localized regions focally we can examine the effect of their absence in comparison to intact areas of the same animal. We will chiefly examine the consequences of radial glial elimination through cell proliferation assays, analysis of cell migration by pulse-chase studies, specific immunolabeling, and anatomical tract tracing methods. Successful ablation of radial glia will allow us to investigate the involvement of this cell class in multiple distinct development processes. Initially, we will focus on the proliferative and migratory activity that occurs in the postnatal subventricular zone, where most of the cell bodies of the radial glial cells are found at this stage.
