title: Drosophila ciD encodes a hybrid Pangolin/Cubitus interruptus protein that diverts the Wingless into the Hedgehog signaling pathway.
abstract: The Hedgehog (Hh) and Wingless (Wg) signaling pathways play important roles in animal development. The activities of the two pathways depend on each other during Drosophila embryogenesis. In the embryonic segment, Wg is required in anterior cells to sustain Hh secretion in adjacent posterior cells. Hh input in turn is necessary for anterior cells to maintain wg expression. The Hh and Wg pathways are mediated by the transcription factors Cubitus interruptus (Ci) and Pangolin/TCF (Pan), respectively. Coincidentally, pan and ci are adjacent genes on the fourth chromosome in a head-to-head orientation. Our genetic and in situ hybridization data indicate that ciD is a mutation affecting both ci and pan. Molecular analysis revealed that the ciD allele is caused by an inversion event that swapped the promoter regions and the first exons of the two genes. The ci gene in ciD is controlled by the ubiquitous pan promoter and encodes a hybrid Ci protein that carries the N-terminal region of Pan. This domain has previously been shown to bind to the b-catenin homolog Armadillo (Arm), raising the possibility that Wg input, in addition to Hh input, modulates the activity of the hybrid CiD protein. Indeed, we found that Wg signaling induces the expression of the Hh target gene patched (ptc) in ciD animals. We provide evidence that this effect depends on the ability of the CiD protein to bind Arm. Genetic and molecular data indicate that wild-type Pan and CiD compete for binding to Arm, leading to a compromised transduction of the Wg signal in heterozygous ciD/+ animals and to a dramatic enhancement of the gain-of-function activity of CiD in homozygous mutants. Thus, the Hh and the Wg pathways are affected by the ciD mutation, and the CiD fusion protein integrates the activities of both.
authors.affiliation: Zoologisches Institut, Universität Zürich, 8057, Zurich, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Schweizer
authors.forename: K
authors.initials: K
authors.lastname: Basler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D007446:Chromosome Inversion; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005796:Genes; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000235:genetics* / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D019076:Transgenes; D014921:Wings, Animal / Q000196:embryology* / Q000648:ultrastructure; D051155:Wnt1 Protein
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C092937:ci protein, Drosophila; C115159:pan protein, Drosophila; C070844:ptc protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila