THE DROSOPHILA BROAD-COMPLEX PLAYS A KEY ROLE IN CONTROLLING ECDYSONE-REGULATED GENE-EXPRESSION AT THE ONSET OF METAMORPHOSIS

During Drosophila third instar larval development, one or more pulses of the steroid hormone ecdysone activate three temporally distinct set s of genes in the salivary glands, represented by puffs in the polyten e chromosomes. The intermolt genes are induced first, in mid-third ins tar larvae; these genes encode a protein glue used by the animal to ad here itself to a solid substrate for metamorphosis. The intermolt gene s are repressed at puparium formation as a high titer ecdysone pulse d irectly induces a small set of early regulatory genes. The early genes both repress their own expression and activate more than 100 late sec ondary-response genes. The Broad-Complex (BR-C) is an early ecdysone-i nducible gene that encodes a family of DNA binding proteins defined by at least three lethal complementation groups: br, rbp, and l(1)2Bc. W e have found that the BR-C is critical for the appropriate regulation of all three classes of ecdysone-inducible genes. Both rbp and l(1)2Bc are required for glue gene induction in mid-third instar larvae. In a ddition, the l(1)2Bc function is required for glue gene repression in prepupae; in l(1)2Bc mutants the glue genes are re-induced by the late prepupal ecdysone pulse, recapitulating a mid-third instar regulatory response at an inappropriate stage in development. The l(1)2Bc functi on is also required for the complete ecdysone induction of some early mRNAs (E74A, E75A, and BR-C) and efficient repression of most early mR NAs in prepupae. Like the intermolt secondary-response genes, the late secondary-response genes are absolutely dependent on rbp for their in duction. An effect of l(1)2Bc mutations on late gene activity can also be detected, but is most likely a secondary consequence of the submax imal ecdysone-induction of a subset of early regulatory products. Our results indicate that the BR-C plays a key role in dictating the stage -specificity or the ecdysone response. In addition, the ecdysone-recep tor protein complex alone is not sufficient for appropriate induction of the early primary-response genes, but requires the prior expression of BR-C proteins. These studies define the BR-C as a kev regulator of gene activity at the onset of metamorphosis in Drosophila.