The expression of many genes is under the control of """"""""regulatory genes"""""""" whose products are required as transcription factors to selectively turn on and off gene expression. This project will evaluate the potential effects of specific environmental agents on these transcription factors and how such effects may influence changes in target genes and subsequent gene products. The developing nervous system expresses a very high number of genes which are necessary to bring about the successful execution of the developmental program. Any alterations in this process could have a major impact on the developmental cascade of the nervous system. This project will be conducted in vivo (in the postnatally developing rat) and in vitro (primary cell cultures of cerebellar granule cells and oligodendroglia). In situ hybridization and immunohistochemical analysis will be conducted to determine the relationship between cell types in the nervous system and the subsequent alterations following toxicant exposure which may account for the observed neurotoxic effect. During the developmental process, genes which play a critical role as transcription factors may be regulated differently than in the mature nervous system. This project will examine the possible differences in regulation of transcription factors and the role that it may play in the differential vulnerability of the developing organism.
