The secreted molecule encoded by hedgehog (hh) plays a central role in patterning the developing Drosophila epithelium. Genetic screens have identified a number of genes now shown to comprise the Hh signaling pathway. Subsequent studies in vertebrates have demonstrated that the Hh pathway is conserved. Moreover, defects in the Hh signaling pathway have been shown to correlate with the onset of cancer in humans. Large-scale genetic screens in the Perrirnon lab have identified a number of new genes with segment polarity phenotypes. I have begun to analyze one of these genes called 7F21. My preliminary results suggest that 7F21 is required for Hh signal transduction. The experiments in this proposal are designed to fully characterize 7F21 by phenotypic and molecular criteria. Further, I describe a unique genetic screen designed to identify new Hh target genes that directly regulate cell adhesion. The goal of this proposal is to identify and characterize new molecules involved in epithelial patterning and in the pathogenesis of human cancers.