Hormone signaling is required in a variety of developmental processes in a host of animals, from insects to humans. Defects in hormones and their receptors are associated with many medical defects and diseases, including cancers, developmental and reproductive disorders. The receptors of these hormones function as ligand activated transcriptional regulators (Evans, 1988). The fact that these hormone molecules initiate so many specialized and tightly regulated mechanisms, makes the investigation and elucidation of these pathways an extremely complicated endeavor. For this task the Drosophila animal system has been recruited for its economical and efficient means of genetic manipulation. The steroid hormone ecdysone acts to trigger molting and metamorphosis during Drosophila development. Ecdysone pulses occur at very specific intervals and at definite concentration levels during Drosophila development. The only known receptor molecule for ecdysone, ecdysone receptor protein (EcR), is a nuclear receptor that [along with its heterodimeric partner, ultraspiracle protein (USP)] binds ecdysone and promotes the transcription of target genes. There are at least three isoforms of the EcR protein, (EcR-A, EcR-B1, and EcR-B2) and each is hypothesized to have separate spatial and/or temporal activities, based on their unique expression patterns (Talbot. 1993), and their unique mutant phenotype analyses (Bender, 1997). This data suggests that the isoforms play a key role in the coordination of the correct signaling paths induced by ecdysone. The goals of this project are to molecularly determine the requirements of the EcR-A during Drosophila melanogaster development.

F31GM020095

1999-12-01

1900-01-01