title: Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning.
abstract: Defining the three body axes is a central event of vertebrate morphogenesis. Establishment of left-right (L-R) asymmetry in development follows the determination of dorsal-ventral and anterior-posterior (A-P) body axes, although the molecular mechanism underlying precise L-R symmetry breaking in reference to the other two axes is still poorly understood. Here, by removing both Vangl1 and Vangl2, the two mouse homologues of a Drosophila core planar cell polarity (PCP) gene Van Gogh (Vang), we reveal a previously unrecognized function of PCP in the initial breaking of lateral symmetry. The leftward nodal flow across the posterior notochord (PNC) has been identified as the earliest event in the de novo formation of L-R asymmetry. We show that PCP is essential in interpreting the A-P patterning information and linking it to L-R asymmetry. In the absence of Vangl1 and Vangl2, cilia are positioned randomly around the centre of the PNC cells and nodal flow is turbulent, which results in disrupted L-R asymmetry. PCP in mouse, unlike what has been implicated in other vertebrate species, is not required for ciliogenesis, cilium motility, Sonic hedgehog (Shh) signalling or apical docking of basal bodies in ciliated tracheal epithelial cells. Our data suggest that PCP acts earlier than the unidirectional nodal flow during bilateral symmetry breaking in vertebrates and provide insight into the functional mechanism of PCP in organizing the vertebrate tissues in development.
authors.affiliation: Developmental Genetics Section, Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Song
authors.forename: Jianxin
authors.initials: J
authors.lastname: Hu
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Gene
authors.initials: G
authors.lastname: Elliott
authors.forename: Philipp
authors.initials: P
authors.lastname: Andre
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000483:Alleles; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D002923:Cilia / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D007839:Functional Laterality / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C431577:Ltap protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C528120:Vangl1 protein, mouse