title: Ankrd6 is a mammalian functional homolog of Drosophila planar cell polarity gene diego and regulates coordinated cellular orientation in the mouse inner ear.
abstract: The coordinated polarization of neighboring cells within the plane of the tissue, known as planar cell polarity (PCP), is a recurring theme in biology. It is required for numerous developmental processes for the form and function of many tissues and organs across species. The genetic pathway regulating PCP was first discovered in Drosophila, and an analogous but distinct pathway is emerging in vertebrates. It consists of membrane protein complexes known as core PCP proteins that are conserved across species. Here we report that the over-expression of the murine Ankrd6 (mAnkrd6) gene that shares homology with Drosophila core PCP gene diego causes a typical PCP phenotype in Drosophila, and mAnkrd6 can rescue the loss of function of diego in Drosophila. In mice, mAnkrd6 protein is asymmetrically localized in cells of the inner ear sensory organs, characteristic of components of conserved core PCP complexes. The loss of mAnkrd6 causes PCP defects in the inner ear sensory organs. Moreover, canonical Wnt signaling is significantly increased in mouse embryonic fibroblasts from mAnkrd6 knockout mice in comparison to wild type controls. Together, these results indicated that mAnkrd6 is a functional homolog of the Drosophila diego gene for mammalian PCP regulation and act to suppress canonical Wnt signaling.
authors.affiliation: Department of Cell Biology, Emory University, Atlanta, GA 30322, USA. Electronic address: C.Jones@wellcome.ac.uk.
authors.forename: Chonnettia
authors.initials: C
authors.lastname: Jones
authors.affiliation: Department of Cell Biology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Qian
authors.affiliation: Department of Cell Biology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Sun Myoung
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Cell Biology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Shuangding
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ren
authors.affiliation: Department of Cell Biology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Knapp
authors.affiliation: Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Sprinzak
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Karen B
authors.initials: KB
authors.lastname: Avraham
authors.affiliation: Laboratory of Cell Asymmetry, Center for Developmental Biology, Riken, Kobe, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuzaki
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China.
authors.forename: Fanglu
authors.initials: F
authors.lastname: Chi
authors.affiliation: Department of Cell Biology, Emory University, Atlanta, GA 30322, USA. Electronic address: ping.chen@emory.edu.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D007758:Ear, Inner / Q000166:cytology / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology
chemical_list: C464903:Ankrd6 protein, mouse; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C492998:Dgo protein, Drosophila; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins
keywords: Ankrd6; Diego; Diversin; Inner ear; Inversin; PCP