CELL-TYPE-SPECIFIC DEVELOPMENT OF RODENT CENTRAL-NERVOUS-SYSTEM PROGENITOR CELLS IN CULTURE

Object. The aim of the study was to assess the pluripotential central nervous system (CNS) progenitor cells that give rise to the many diffe rentiated neuronal and glial cell types of the adult mammalian brain a nd the role of peptide growth factors such as the epidermal growth fac tor (EGF) and basic fibroblast growth factor (bFGF). The action of the se factors is crucial to the survival and ultimate differentiation of these CNS progenitor cells. However, the precise role of EGF and bFGF in the time course of cellular development, the acquisition of cell ty pe specificity, and possible differential mitogenic behavior has not b een clearly defined. Methods. The authors defined the time course of C NS progenitor cell development in cultured embryonic rodent cells by u sing immunocytochemical analysis to identify the expression of pluripo tential (nestin)-, neuron (microtubule-associated protein-2 [MAP-2])-, and glia (glial fibrillary acidic protein [GFAP])-specific proteins i n response to treatment with EGF and bFGF alone or in combination. The bromodeoxyuridine (BUdR) labeling index for each treatment group was used to define the mitogenic effects of each growth factor. In this in vestigation, the authors observed that progenitor cells develop in a s tereotypical fashion when exposed to bFGF or EGF. Marked staining for nestin was evident soon after plating. This declined over time as stai ning for MAP-2 and GFAP increased. When treated with EGF alone, cells maintained their nestin immunoreactivity longer than those treated wit h bFGF alone or in combination with EGF. Treatment with bFGF alone pro moted a significant increase in MAP-2 and, to a much lesser extent, GF AP reactivity. This was observed concomitant with the decline in nesti n staining. The BUdR labeling index was similar among the different tr eatment groups and declined similarly over time in all treatment group s. Conclusions. The effects of EGF and/or bFGF on the expression of de velopment-and lineage-specific markers likely reflect the specific eff ects of these factors on developmental processes. These data indicate that bFGF exerts a preferential effect on neuronal development and, to a lesser extent, glial development, which is not explained by selecti ve mitogenicity. The persistence of nestin staining seen in the cells treated with EGF alone indicates that EGF may function as a stem cell survival factor. This study provides evidence that CNS cell type-speci fic development can be altered by the manipulation of peptide growth f actors that act as differentiation agents.