Downregulation of the tissue-specific transcription factor Fork head by Broad-Complex mediates a stage-specific hormone response

Drosophila development is coordinated by pulses of the steroid hormone 20-h ydroxyeedysone (20E). During metamorphosis, the 20E-inducible Broad-Complex (BR-C) gene plays a key role in the genetic hierarchies that transduce the hormone signal, being required for the destruction of larval tissues and n umerous aspects of adult development. Most of the known BR-C target genes, including the salivary gland secretion protein (Sgs) genes, are terminal di fferentiation genes that are thought to be directly regulated by BR-C-encod ed transcription factors. Here, we show that repression of Sgs expression i s indirectly controlled by the BR-C through transcriptional down-regulation of fork head, a tissue-specific gene that plays a central role in salivary gland development and is required for Sgs expression. Our results demonstr ate that integration of a tissue-specific regulatory gene into a 20E-contro lled genetic hierarchy provides a mechanism for hormonal repression. Furthe rmore, they suggest that the BR-C is placed at a different position within the 20E-controlled hierarchies than previously assumed, and that at least p art of its pleiotropic functions are mediated by tissue-specific regulators .