Mechanisms by which Distal-less performs distinct functions during Drosophila appendage development

This thesis elucidates the genetic and molecular mechanisms by which the Drosophila antenna and leg primordia become specified and patterned into morphologically and functionally distinct structures. I focused particularly on the functions of Distal-less, and how it is involved in proximodistal patterning and antennal fate determination.; bric a brac is a Distal-less downstream target required for distal joint formation. The distinct combinations of Distal-less, Homothorax and Dachshund in the antenna and leg differentially regulate bric a brac. This differential regulation of bric a brac contributes to the different distal joint numbers of the antenna and leg. Thus one of the phenotypic consequences resulting from varying genetic regulatory relationships is that the distal segment numbers of antenna and leg are different. Since the numbers of distal segments are diverse among insects, the comparative studies between antenna and leg provide a model for how morphologically distinct appendages may have evolved.; I next investigated the molecular machinery by which Distal-less specifies antenna fate. I found Distal-less synergistically interacts with homothorax during antenna development. I demonstrated both in vitro and in vivo that Distal-less interacts physically with Extradenticle, a known partner for Homothorax, and that all three can form protein complexes. Moreover, different aspects of antenna development are activated when distinct combinations of Distal-less, Extradenticle and Homothorax are provided. My findings suggest that different antenna genes have different types of enhancers. The differential and combinatorial use of suites of transcription factors facilitates distinct transcriptional outcomes during specification of a complex tissue. I also provide evidence that underscores the necessity for spatiotemporal changes in Homothorax and Extradenticle expression, and propose that these changes are critical for Distal-less to perform both distal patterning function and antenna fate specification. Distal-less alone activates a distal patterning program, while Distal-less, Extradenticle and Homothorax likely form a variety of complexes that differentially regulate subclasses of antenna-specific targets. Since most homeodomain proteins have more than one function during development, my work offers a mechanism by which different functions are carried out by the same gene in a single tissue.