Broad specifies pupal development

Molting and metamorphosis in insects are under the control of two hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH) (Riddiford, 1994) [We use the term ‘ecdysone’ as a generic term to refer to the natural ecdysteroids that cause molting and metamorphosis, primarily α-ecdysone and its metabolite 20-hydroxyecdysone (Riddiford et al., 2001).] Ecdysone induces and coordinates molting, but the character of the molt is determined by JH. In the presence of JH, there is no change in form; in the absence of JH, ecdysone causes the switching in gene expression necessary for metamorphosis, first to the pupa, then to the adult. JH therefore prevents this switching action of ecdysone and thus maintains the ‘status quo’ during a molt (Williams, 1961). In the Coleoptera and in Lepidoptera such as the tobacco hornworm, Manduca sexta, where the epidermis makes sequentially several larval cuticles, the pupal cuticle and finally the adult cuticle, JH prevents each of the metamorphic transitions (Riddiford, 1995; Willis, 1996). By contrast, in Drosophila and the other higher flies, the pupal epidermis, except for the abdomen, is derived from imaginal discs, and exogenous JH does not prevent the larval-pupal transformation, even when given throughout larval life (Ashburner, 1970; Postlethwait, 1974; Riddiford and Ashburner, 1991). Nor does JH have any effect on the subsequent adult differentiation of the head and thorax externally, although it disrupts metamorphosis of the nervous and muscular systems when given during the prepupal period (Restifo and Wilson, 1998). JH application during the final larval instar or during the prepupal period, however, prevents the normal adult differentiation of the abdomen (Ashburner, 1970; Postlethwait, 1974; Riddiford and Ashburner, 1991), whose cells arise from proliferation of the histoblasts during the prepupal period (Madhavan and Madhavan, 1980). In Drosophila melanogaster the ecdysone-induced Broad (BR; previously called the Broad-Complex or BR-C) transcription factors are essential for the onset of metamorphosis since the amorphic broad (br) mutant npr can develop normally to the final larval instar but cannot undergo metamorphosis (Kiss et al., 1976; Kiss et al., 1988). The BR proteins are members of the Broad-Tramtrack-Bric-a-brac (BTB) family of transcription factors that share a common Nterminal domain thought to be important in protein-protein interactions (Zollman et al., 1994). The alternately spliced C terminus contains one of four pairs of C2H2 DNA-binding zinc fingers (Z1, Z2, Z3, Z4), and there are three variants of the Z1 isoform generated by alternative splicing in the linker between 2259 Development 129, 2259-2269 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV7940