title: Pkd1l1 complexes with Pkd2 on motile cilia and functions to establish the left-right axis.
abstract: The internal organs of vertebrates show distinctive left-right asymmetry. Leftward extracellular fluid flow at the node (nodal flow), which is generated by the rotational movement of node cilia, is essential for left-right patterning in the mouse and other vertebrates. However, the identity of the pathways by which nodal flow is interpreted remains controversial as the molecular sensors of this process are unknown. In the current study, we show that the medaka left-right mutant abecobe (abc) is defective for left-right asymmetric expression of southpaw, lefty and charon, but not for nodal flow. We identify the abc gene as pkd1l1, the expression of which is confined to Kupffer's vesicle (KV, an organ equivalent to the node). Pkd1l1 can interact and interdependently colocalize with Pkd2 at the cilia in KV. We further demonstrate that all KV cilia contain Pkd1l1 and Pkd2 and left-right dynein, and that they are motile. These results suggest that Pkd1l1 and Pkd2 form a complex that functions as the nodal flow sensor in the motile cilia of the medaka KV. We propose a new model for the role of cilia in left-right patterning in which the KV cilia have a dual function: to generate nodal flow and to interpret it through Pkd1l1-Pkd2 complexes.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Uehara
authors.forename: Sumito
authors.initials: S
authors.lastname: Koshida
authors.forename: Norio
authors.initials: N
authors.lastname: Iijima
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.forename: Takahiko
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002923:Cilia / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D009068:Movement / Q000502:physiology; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009990:Oryzias / Q000196:embryology / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D046912:Multiprotein Complexes; D050396:TRPP Cation Channels