DROSOPHILA CUBITUS INTERRUPTUS FORMS A NEGATIVE FEEDBACK LOOP WITH PATCHED AND REGULATES EXPRESSION OF HEDGEHOG TARGET GENES

The Drosophila segment polarity gene cubitus interruptus (ci) encodes a zinc finger protein that is required for the proper patterning of se gments and imaginal discs. Epistasis analysis indicates that ci functi ons in the Hedgehog (Hh) signal transduction pathway and is required t o maintain wingless expression in the embryo, In this paper, the role of the Ci protein in the Hh signaling pathway is examined in more deta il. Our results show that ectopic expression of ci in imaginal discs a nd the embryo activates the expression of Hh target genes, One of thes e target genes, patched, forms a negative feedback loop with ci that i s regulated by Hh signal transduction, Activation is also achieved usi ng the Ci zinc finger domain fused to a heterologous transactivation d omain. Conversely, repression of Hh target genes occurs in animals exp ressing the Ci zinc finger domain fused to a repression domain, To exa mine Ci function in more detail, regions of the Ci protein that are re sponsible for its ability to transactivate and its subcellular distrib ution have been identified.