title: Lack of a laterality phenotype in Pkd1 knock-out embryos correlates with absence of polycystin-1 in nodal cilia.
abstract: The invariant asymmetric placement of thoracic and abdominal organs in the vertebrates is controlled by the left-asymmetric activity of the Nodal signaling cascade during embryogenesis. In the mouse embryo asymmetric induction of nodal is thought to be dependent on functional monocilia on the ventral node cells and on the Pkd2 gene, which encodes the calcium channel polycystin-2 (PC2). In humans mutations in PKD2 and PKD1 give rise to polycystic kidney disease. The PC1 and PC2 proteins are thought to function as part of a multifactorial complex. Localization of both proteins to the primary renal cilium suggested a function on cilia of the ventral node. Here we investigated Pkd1 knock-out embryos for laterality defects and found wild-type organ morphogenesis and normal expression of nodal and Pitx2. While PC2 localized to nodal cilia, no ciliary localization of PC1 was detected in mouse embryos. This finding was confirmed in an archetypical mammalian blastodisc, the rabbit embryo. Thus, absence of PC1 localization to cilia corresponded with a lack of laterality defects in Pkd1 knock-out embryos. Our results demonstrate a PC1-independent function of PC2 in left-right axis formation, and indirectly support a ciliary role of PC2 in this process.
authors.affiliation: Institut für Zoologie (220), Universität Hohenheim, Garbenstr. 30, D-70593 Stuttgart, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Karcher
authors.forename: Anja
authors.initials: A
authors.lastname: Fischer
authors.forename: Axel
authors.initials: A
authors.lastname: Schweickert
authors.forename: Eva
authors.initials: E
authors.lastname: Bitzer
authors.forename: Shigeo
authors.initials: S
authors.lastname: Horie
authors.forename: Ralph
authors.initials: R
authors.lastname: Witzgall
authors.forename: Martin
authors.initials: M
authors.lastname: Blum
mesh_terms: D000818:Animals; D002923:Cilia / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D055457:Nodal Protein; D009687:Nuclear Proteins / Q000378:metabolism*; D011506:Proteins / Q000235:genetics*; D011817:Rabbits; D050396:TRPP Cation Channels; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D008565:Membrane Proteins; D055457:Nodal Protein; D009687:Nuclear Proteins; D011506:Proteins; D050396:TRPP Cation Channels; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000097577:Homeobox Protein PITX2; C526007:NODAL protein, human; C526008:Nodal protein, mouse