This research proposal addresses a novel mechanism by which retinoic acid receptor positively or negatively regulates the development of the central nervous system in response to morphogen (e.g., retinoic acid). The objective of this work is to examine the hypothesis that specific effects of retinoic acid in the development and homeostasis of the central nervous system are dictated by novel cell-specific, polarity- specific factor(s) that interact with the retinoic acid receptor. The specific aims are: 1) to construct cDNA expression libraries for screening, 2) to identify putative cell-specific and polarity-specific factor(s) using a functional screen, and 3) to characterize candidates to be considered to function as a cell-specific and polarity-specific factor in neuron. The identification of polarity-specific and cell- specific regulators of retinoic acid receptor function would provide an explanation of differential responses to morphogens by subset of potential target genes, and the regulation of these cell-specific regulators would become and important area of future research.