title: Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog.
abstract: While components of the pathway that establishes left-right asymmetry have been identified in diverse animals, from vertebrates to flies, it is striking that the genes involved in the first symmetry-breaking step remain wholly unknown in the most obviously chiral animals, the gastropod snails. Previously, research on snails was used to show that left-right signaling of Nodal, downstream of symmetry breaking, may be an ancestral feature of the Bilateria [1 and 2]. Here, we report that a disabling mutation in one copy of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry breaking in the pond snail. This is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to a sinistral phenocopy, and in frogs, drug inhibition or overexpression by microinjection of formin has a chirality-randomizing effect in early (pre-cilia) embryos. Contrary to expectations based on existing models [3, 4 and 5], we discovered asymmetric gene expression in 2- and 4-cell snail embryos, preceding morphological asymmetry. As the formin-actin filament has been shown to be part of an asymmetry-breaking switch in vitro [6 and 7], together these results are consistent with the view that animals with diverse body plans may derive their asymmetries from the same intracellular chiral elements [8].
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK. Electronic address: angus.davison@nottingham.ac.uk.
authors.forename: Angus
authors.initials: A
authors.lastname: Davison
authors.affiliation: Center for Regenerative and Developmental Biology, and Department of Biology, Tufts University, Medford, MA 02155, USA.
authors.forename: Gary S
authors.initials: GS
authors.lastname: McDowell
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Holden
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Harriet F
authors.initials: HF
authors.lastname: Johnson
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Georgios D
authors.initials: GD
authors.lastname: Koutsovoulos
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: M Maureen
authors.initials: MM
authors.lastname: Liu
authors.affiliation: Department for Biomedical Molecular Biology, Ghent University, and Inflammation Research Center (IRC), VIB, 9052 Ghent, Belgium.
authors.forename: Paco
authors.initials: P
authors.lastname: Hulpiau
authors.affiliation: Department for Biomedical Molecular Biology, Ghent University, and Inflammation Research Center (IRC), VIB, 9052 Ghent, Belgium.
authors.forename: Frans
authors.initials: F
authors.lastname: Van Roy
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Wade
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Ruby
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Fengtang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Community and Ecosystem Ecology, Division of Ecology and Evolutionary Biology, Graduate School of Life Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Chiba
authors.affiliation: Department for Biomedical Molecular Biology, Ghent University, and Inflammation Research Center (IRC), VIB, 9052 Ghent, Belgium.
authors.forename: John W
authors.initials: JW
authors.lastname: Davey
authors.affiliation: Department of Geobiology, University of Göttingen, Göttingen 37077, Germany.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Jackson
authors.affiliation: Center for Regenerative and Developmental Biology, and Department of Biology, Tufts University, Medford, MA 02155, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3JT, UK; Edinburgh Genomics, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Blaxter
mesh_terms: D000818:Animals; D019521:Body Patterning; D005326:Fetal Proteins / Q000235:genetics* / Q000378:metabolism; D000080865:Formins; D008195:Lymnaea / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics* / Q000378:metabolism
chemical_list: D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins