Vertebrate homologs of Drosophila suppressor of fused interact with the Gli family of transcriptional regulators

The hedgehog (Hh) signaling pathway is crucial for pattern formation during metazoan development. Although originially characterized in Drosophila, ve rtebrate homologs have been identified for several, but not all, genes in t he pathway. Analysis of mutants in Drosophila demonstrates that Suppressor of fused [Su(fu)] interacts genetically with genes encoding proteins in the Hh signal transduction pathway, and its protein product physically interac ts with two of the proteins in the Hh pathway. We report here the molecular cloning and characterization of chicken and mouse homologs of Su(fu). The chick and mouse proteins are 27% identical and 53% similar at the amino aci d level to the Drosophila melanogaster and Drosophila virilis proteins. Ver tebrate Su(fu) is widely expressed in the developing embryo with higher lev els in tissues that are known to be patterned by Hh signaling. The chick Su (fu) protein can physically interact with factors known to function in Hh s ignal transduction including the Drosophila serine/threonine kinase, Fused, and the vertebrate transcriptional regulators Gli1 and Gli3. This interact ion may be significant for transcriptional regulation, as recombinant Su(fu ) enhances the ability of Gli proteins to bind DNA in electrophoretic mobil ity shift assays. (C) 1999 Academic Press.