PATCHED OVEREXPRESSION ALTERS WING DISC SIZE AND PATTERN - TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL EFFECTS ON HEDGEHOG TARGETS

The membrane protein, Patched, plays a critical role in patterning emb ryonic and imaginal tissues in Drosophila. patched constitutively inac tivates the transcription of target genes such as wingless, decapentap legic, and patched itself, The secreted protein, Hedgehog, induces tra nscription of target genes by opposing the Patched signaling pathway, Using the Ga14 UAS system we have overexpressed patched in wing imagin al discs and found that high Patched levels, expressed in either norma l or ectopic patterns, result in loss of wing vein patterning in both compartments centering at the anterior/posterior border, In addition, patched inhibits the formation of the mechanosensory neurons, the camp aniform sensilla, in the wing blade, The patched wing vein phenotype i s modulated by mutations in hedgehog and cubitus interruptus (ci), Pat ched overexpression inhibits transcription of patched and decapentaple gic and post-transcriptionally decreases the amount of Ci protein at t he anterior/posterior boundary. In hedgehog(Mn) wing discs, which expr ess ectopic hedgehog, Ci levels are correspondingly elevated, suggesti ng that hedgehog relieves patched repression of Ci accumulation, Prote in kinase A also regulates Ci; protein kinase A mutant clones in the a nterior compartment have increased levels of Ci protein, Thus patched influences wing disc patterning by decreasing Ci protein levels and in activating hedgehog target genes in the anterior compartment.