HEDGEHOG SIGNALING REGULATES TRANSCRIPTION THROUGH CUBITUS INTERRUPTUS, A SEQUENCE-SPECIFIC DNA-BINDING PROTEIN

Hedgehog (Hh) is a member of a family of secreted proteins that direct patterning at multiple stages in both Drosophila and vertebrate devel opment. During Drosophila embryogenesis, Hh protein is secreted by the cells of the posterior compartment of each segment. Hh activates tran scription of wingless (log), gooseberry (gsb), and patched (ptc) in th e cells immediately adjacent to Db-secreting cells. Hh signaling is th ought to involve the segment polarity gene cubitus interruptus (ci). c i encodes a zinc finger protein of the Gli family of sequence-specific DNA binding proteins, ci mRNA is expressed in all non-Hh expressing c ells. Here we demonstrate ci activity is both necessary and sufficient to drive expression of I-Ih-responsive genes in the Drosophila embryo s, We show that Ci is a sequence-specific DNA binding protein that dri ves transcription from the wg promoter in transiently transfected cell s, We demonstrate that Ci binding sites in the log promoter are necess ary for this transcriptional activation, These data taken together pro vide strong evidence that Ci is a transcriptional effector of Hh signa ling.