Extensive studies of nuclear hormone receptors have transformed the field of molecular endocrinology, leading to new insights into how these ligand-regulated transcription factors control a broad range of biological programs. In spite of these significant advances, however, a number of important questions remain. Central among these is how temporal specificity is achieved in hormone signaling. How do repeated pulses of the same hormone direct different genetic and biological responses at different times? I propose to address this question by using Drosophila as a model system, focusing on the role of the prepupal competence factor and orphan nuclear receptor betaFTZ-F1 in providing temporal specificity to pulses of the steroid hormone ecdysone during metamorphosis. I will use microarrays to obtain genome wide expression profiles from ecdysone-treated organ cultures of wild-type animals and from both gain-of-function and loss-of-function betaFTZ-F1 mutants. These studies will lead to the identification of genes that are regulated by ecdysone in a stage-specific manner, responding to only the prepupal ecdysone pulse and dependent on the betaFTZ-F1 competence factor. Several of these genes will be selected for detailed functional analysis to determine their biological roles at this stage in development. The studies proposed here will provide new insights into the molecular mechanisms of competence for steroid responses as well as a basis for understanding how temporal specificity is achieved in hormone signaling pathways.
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