Formin Is Associated With Left-Right Asymmetry in the Pond Snail and the Frog

Curr Biol. 2016 Mar 7;26(5):654-60. doi: 10.1016/j.cub.2015.12.071. Epub 2016 Feb 25.

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].

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning*
  • Fetal Proteins / genetics*
  • Fetal Proteins / metabolism
  • Formins
  • Lymnaea / embryology
  • Lymnaea / genetics*
  • Lymnaea / metabolism
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Phenotype
  • Signal Transduction*
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics*
  • Xenopus laevis / metabolism

Substances

  • Fetal Proteins
  • Formins
  • Microfilament Proteins
  • Nuclear Proteins