QUANTITATIVE EFFECTS OF HEDGEHOG AND DECAPENTAPLEGIC ACTIVITY ON THE PATTERNING OF THE DROSOPHILA WING

Background: Members of the hedgehog (hh) gene family encode a novel cl ass of proteins implicated in positional signalling in both invertebra tes and vertebrates. In Drosophila, the hh gene has been shown to regu late patterning of the imaginal discs, the precursors of the insect li mbs. In a remarkably similar fashion, the function and expression of t he sonic hedgehog (shh) gene is closely associated with the 'zone of p olarizing activity' (ZPA) that controls antero-posterior patterning of the vertebrate limb. Both of these functions suggest a role for hedge hog family proteins as morphogens. An alternative possibility, however , is that hh and its homologues act to control the expression of other instructive signalling molecules. Results: We have explored this issu e by examining the effects on Drosophila wing patterning of ectopicall y expressing varying levels of hh and shh, as well as of the putative hh target gene, decapentaplegic (dpp), a member of the transforming gr owth factor-beta family of signalling molecules. We find that differen t levels of hh activity can induce graded changes in the patterning of the wing, and that zebrafish shh acts in a similar though attenuated fashion. Varying levels of ectopic hh and shh activity can differentia lly activate transcription of the patched and dpp genes. Furthermore, ectopic expression of dpp alone is sufficient to induce the pattern al terations caused by ectopic hh or shh activity. Conclusion: Thus, hh f amily proteins can elicit different responses in a dose-dependent mann er in the imaginal disc. The principal function of hh, however, is to activate transcription of dpp at the compartment boundary, thereby est ablishing a source of dpp activity that is the primary determinant of antero-posterior patterning.