Molecular characterization of the singed wings locus of Drosophila melanogaster

BACKGROUND: Hormones frequently guide animal development via the induction of cascades of gene activities, whose products further amplify an initial hormonal stimulus. In Drosophila the transformation of the larva into the pupa and the subsequent metamorphosis to the adult stage is triggered by changes in the titer of the steroid hormone 20-hydroxyecdysone. singed wings (swi) is the only gene known in Drosophila melanogaster for which mutations specifically interrupt the transmission of the regulatory signal from early to late ecdysone inducible genes. RESULTS: We have characterized singed wings locus, showing it to correspond to EG:171E4.2 (CG3095). swi encodes a predicted 68.5-kDa protein that contains N-terminal histidine-rich and threonine-rich domains, a cysteine-rich C-terminal region and two leucine-rich repeats. The SWI protein has a close homolog in D. melanogaster, defining a new family of SWI-like proteins, and is conserved in D. pseudoobscura. A lethal mutation, swi(t476), shows a severe disruption of the ecdysone pathway and is a C>Y substitution in one of the two conserved CysXCys motifs that are common to SWI and the Drosophila Toll-4 protein. CONCLUSIONS: It is not entirely clear from the present molecular analysis how the SWI protein may function in the ecdysone induced cascade. Currently all predictions agree in that SWI is very unlikely to be a nuclear protein. Thus it probably exercises its control of "late" ecdysone genes indirectly. Apparently the genetic regulation of ecdysone signaling is much more complex then was previously anticipated.