| Steroid hormones are potent mediators of many developmental processes, and they can influence tumor progression in cancers of the breast, prostate, and uterine lining. It is also known that steroids exert their biological effects by binding with nuclear receptors to directly mediate changes in gene transcription. However, little is known about how these generalized signalling molecules elicit a tissue-specific response in developing target tissues.; In Drosophila, a single steroid hormone, 20-hydroxyecdysone (ecdysone), mediates the major developmental transitions—cuticle molting, metamorphosis—as well as the tissue-specific response of glue secretion in the salivary glands. The premetamorphic pulse of ecdysone induces a hierarchy of gene expression (polytene chromosome puffing cascade) and glue secretion at the end of the third larval instar. A number of hormone-responsive genes have been cloned from chromosomal puff sites, but their role in regulating secretion has yet to be determined. The major focus of this thesis is to determine if ecdysone mediates glue secretion via the ecdysone-regulated puff genes.; Studies presented here investigate the genomic regulation of vesicle-mediated exocytosis by ecdysone. Results from these studies demonstrate that ecdysone acts through its cognate receptor to mediate secretion. Furthermore, a mutation in the BR-C early gene, which encodes several zinc finger DNA-binding protein isoforms, disrupts the proper temporal regulation of secretion.; The role of a second early gene, E63-1, which encodes an EF hand Ca2+-binding protein, was also analyzed. A genetic interaction between E63-1 and calmodulin was identified in double-stranded interfering RNA experiments. In addition, biochemical studies revealed an association between E63-1 and myosin VI at the molecular level. Based on these observations, we propose a model in which E63-1 acts as a light chain to regulate myosin VI function during glue secretion. |
