title: Genetic evidence that Drosophila frizzled controls planar cell polarity and Armadillo signaling by a common mechanism.
abstract: The frizzled (fz) gene in Drosophila controls two distinct signaling pathways: it directs the planar cell polarization (PCP) of epithelia and it regulates cell fate decisions through Armadillo (Arm) by acting as a receptor for the Wnt protein Wingless (Wg). With the exception of dishevelled (dsh), the genes functioning in these two pathways are distinct. We have taken a genetic approach, based on a series of new and existing fz alleles, for identifying individual amino acids required for PCP or Arm signaling. For each allele, we have attempted to quantify the strength of signaling by phenotypic measurements. For PCP signaling, the defect was measured by counting the number of cells secreting multiple hairs in the wing. We then examined each allele for its ability to participate in Arm signaling by the rescue of fz mutant embryos with maternally provided fz function. For both PCP and Arm signaling we observed a broad range of phenotypes, but for every allele there is a strong correlation between its phenotypic strength in each pathway. Therefore, even though the PCP and Arm signaling pathways are genetically distinct, the set of signaling-defective fz alleles affected both pathways to a similar extent. This suggests that fz controls these two different signaling activities by a common mechanism. In addition, this screen yielded a set of missense mutations that identify amino acids specifically required for fz signaling function.
authors.affiliation: Howard Hughes Medical Institute, Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Povelones
authors.forename: Rob
authors.initials: R
authors.lastname: Howes
authors.forename: Matt
authors.initials: M
authors.lastname: Fish
authors.forename: Roel
authors.initials: R
authors.lastname: Nusse
mesh_terms: D000818:Animals; D051186:Armadillo Domain Proteins / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D016764:Cell Polarity / Q000235:genetics* / Q000502:physiology; D017931:DNA Primers; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D051155:Wnt1 Protein
chemical_list: C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D051155:Wnt1 Protein; C058784:fz protein, Drosophila; C074622:wg protein, Drosophila