title: An inwardly rectifying K+ channel is required for patterning.
abstract: Mutations that disrupt function of the human inwardly rectifying potassium channel KIR2.1 are associated with the craniofacial and digital defects of Andersen-Tawil Syndrome, but the contribution of Kir channels to development is undefined. Deletion of mouse Kir2.1 also causes cleft palate and digital defects. These defects are strikingly similar to phenotypes that result from disrupted TGFβ/BMP signaling. We use Drosophila melanogaster to show that a Kir2.1 homolog, Irk2, affects development by disrupting BMP signaling. Phenotypes of irk2 deficient lines, a mutant irk2 allele, irk2 siRNA and expression of a dominant-negative Irk2 subunit (Irk2DN) all demonstrate that Irk2 function is necessary for development of the adult wing. Compromised Irk2 function causes wing-patterning defects similar to those found when signaling through a Drosophila BMP homolog, Decapentaplegic (Dpp), is disrupted. To determine whether Irk2 plays a role in the Dpp pathway, we generated flies in which both Irk2 and Dpp functions are reduced. Irk2DN phenotypes are enhanced by decreased Dpp signaling. In wild-type flies, Dpp signaling can be detected in stripes along the anterior/posterior boundary of the larval imaginal wing disc. Reducing function of Irk2 with siRNA, an irk2 deletion, or expression of Irk2DN reduces the Dpp signal in the wing disc. As Irk channels contribute to Dpp signaling in flies, a similar role for Kir2.1 in BMP signaling may explain the morphological defects of Andersen-Tawil Syndrome and the Kir2.1 knockout mouse.
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
authors.forename: Giri Raj
authors.initials: GR
authors.lastname: Dahal
authors.forename: Joel
authors.initials: J
authors.lastname: Rawson
authors.forename: Brandon
authors.initials: B
authors.lastname: Gassaway
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kwok
authors.forename: Ying
authors.initials: Y
authors.lastname: Tong
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Ptácek
authors.forename: Emily
authors.initials: E
authors.lastname: Bates
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014921:Wings, Animal / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D034741:RNA, Small Interfering; C064196:dpp protein, Drosophila