title: Tow (Target of Wingless), a novel repressor of the Hedgehog pathway in Drosophila.
abstract: Hedgehog (Hh) signalling plays a crucial role in the development and patterning of many tissues in both vertebrates and invertebrates. Aberrations in this pathway lead to severe developmental defects and cancer. Hh signal transduction in receiving cells is a well studied phenomenon; however questions still remain concerning the mechanism of repression of the pathway activator Smoothened (Smo) in the absence of Hh. Here we describe a novel repressor of the Hh pathway, Target of Wingless (Tow). Tow represents the Drosophila homolog of a conserved uncharacterised protein family. We show that Tow acts in Hh receiving cells, where its overexpression represses all levels of Hh signalling, and that this repression occurs upstream or at the level of Smo and downstream of the Hh receptor Patched (Ptc). In addition, we find that like Ptc, overexpression of Tow causes an accumulation of lipophorin in the wing disc. We demonstrate that loss of tow enhances different ptc alleles in a similar manner to another pathway repressor, Suppressor of Fused (SuFu), possibly through mediating Ptc dependant lipophorin internalisation. Combined, these results demonstrate that Tow is an important novel regulator of the Hh pathway in the wing imaginal disc, and may shed light on the mechanism of Ptc repression of Smo.
authors.affiliation: Institute of Developmental Biology and Cancer Research, CNRS UMR 6543, Centre de Biochimie, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Ayers
authors.forename: Ralph
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Armel
authors.initials: A
authors.lastname: Gallet
authors.forename: Laurent
authors.initials: L
authors.lastname: Ruel
authors.forename: Pascal
authors.initials: P
authors.lastname: Thérond
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017931:DNA Primers; D004330:Drosophila; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000072086:Smoothened Receptor
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; C523289:Tow protein, Drosophila; C070844:ptc protein, Drosophila; C100664:smo protein, Drosophila; C077245:hh protein, Drosophila