Drosophila transcription factor AP-2 in proboscis, leg and brain central complex development

We report loss- and gain-of-function analyses that identify essential roles in development for Drosophila transcription factor AP-2. A mutagenesis scr een yielded 16 lethal point mutant alleles of dAP-2. Null mutants die as ad ults or late pupae with a reduced proboscis, severely shortened legs (simil ar to 30% of normal length) lacking tarsal joints, and disruptions in the p rotocerebral central complex, a brain region critical for locomotion. Seven hypomorphic alleles constitute a phenotypic series yielding hemizygous adu lts with legs ranging from 40-95% of normal length, Hypomorphic alleles sho w additive effects with respect to leg length and viability; and several he teroallelic lines were established. Heteroallelic adults have moderately pe netrant defects that include necrotic leg joints and ectopic growths (somet imes supernumerary antennae) invading medial eye territory. Several dAP-2 a lleles with DNA binding domain missense mutations are null in hemizygotes b ut have dominant negative effects when paired with hypomorphic alleles. In wild-type leg primordia, dAP-2 is restricted to presumptive joints. Ectopic dAP-2 in leg discs can inhibit but not enhance leg elongation indicating t hat functions of dAP-2 in leg outgrowth are region restricted, In wing disc s, ectopic dAP-2 cell autonomously transforms presumptive wing vein epithel ium to ectopic sensory bristles, consistent with an instructive role in sen sory organ development. These findings reveal multiple functions for dAP-2 during morphogenesis of feeding and locomotor appendages and their neural c ircuitry, and provide a new paradigm for understanding AP-2 family transcri ption factors.