A screen for modifiers of decapentaplegic mutant phenotypes identifies lilliputian, the only member of the Fragile-X/Burkitt's lymphoma family of transcription factors in Drosophila melanogaster

The decapentaplegic (dpp) gene directs numerous developmental events in Dro sophila melanogaster: dpp encodes a member of the Transforming Growth Facto r-beta family of secreted signaling molecules. At this time, mechanisms of dpp signaling have not yet been fully described. Therefore we conducted a g enetic screen for new dpp signaling pathway components. The screen exploite d a transvection-dependent dpp, phenotype: heldout wings. The screen genera ted 30 mutations that appear to disrupt transvection at dpp. One of the mut ations is a translocation with a recessive lethal breakpoint in cytological region 23C1-2. Genetic analyses identified a number of mutations allelic t o this breakpoint. The 23C1-2 complementation group includes several mutati ons in the newly discovered gene lilliputian (lilli). lilli mutations that disrupt the transvection-dependent dpp phenotype are also dominant maternal enhancers of recessive embryonic lethal alleles of dpp and screw. lilli zy gotic mutant embryos exhibit a partially ventralized phenotype similar to d pp embryonic lethal mutations. Phylogenetic analyses revealed that lilli en codes the only Drosophila member of a family of transcription factors that includes the human genes causing Fragile-X mental retardation (FMR2) and Bu rkitt's Lymphoma (LAF4). Taken together, the genetic and phylogenetic data suggest that lilli may be an activator of dpp expression in embryonic dorsa l-ventral patterning and wing development.