title: An absolute requirement for Cubitus interruptus in Hedgehog signaling.
abstract: Hedgehog (Hh) proteins play diverse organizing roles in animal development by regulating gene expression in responding cells. Several components of the Hh signal transduction pathway have been identified, yet their precise role in mediating the various outputs of the pathway is still poorly understood. The Gli homolog Cubitus interruptus (Ci) is involved in controlling the transcription of Drosophila Hh target genes and thus represents the most downstream component known in this pathway. We address the question of whether the Hh pathway is distally branched or, in other words, whether the regulation of Ci activity is the sole output of Hh signaling. Putative Ci-independent branches of Hh signaling are explored by analyzing the behavior of cells that lack Ci but have undergone maximal activation of the Hh transduction pathway due to the removal of Patched (Ptc). The analysis of target gene expression and morphogenetic read-outs of Hh in embryonic, larval and adult stages indicates that Ci is absolutely required for all examined aspects of Hh outputs. We interpret this as evidence against the existence of Ci-independent branches in the Hh signal transduction pathway and propose that most cases of apparent Ci/Gli-independent Hh output can be attributed to the derepression of target gene expression in the absence of Ci/Gli repressor function.
authors.affiliation: Institut für Molekularbiologie, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Méthot
authors.forename: K
authors.initials: K
authors.lastname: Basler
mesh_terms: D000818:Animals; D019521:Body Patterning; D002448:Cell Adhesion; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000254:growth & development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D014921:Wings, Animal / Q000033:anatomy & histology / Q000254:growth & development; D051155:Wnt1 Protein
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C063459:En protein, Drosophila; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D051155:Wnt1 Protein; C092937:ci protein, Drosophila; C064196:dpp protein, Drosophila; C070844:ptc protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila