Mechanism of Nodal Flow: A Conserved Symmetry Breaking Event in Left-Right Axis Determination

Cell. 2005 May 20;121(4):633-644. doi: 10.1016/j.cell.2005.04.008.

Abstract

The leftward flow in extraembryonic fluid is critical for the initial determination of the left-right axis of mouse embryos. It is unclear if this is a conserved mechanism among other vertebrates and how the directionality of the flow arises from the motion of cilia. In this paper, we show that rabbit and medakafish embryos also exhibit a leftward fluid flow in their ventral nodes. In all cases, primary monocilia present a clockwise rotational-like motion. Observations of defective ciliary dynamics in mutant mouse embryos support the idea that the posterior tilt of the cilia during rotational-like beating can explain the leftward fluid flow. Moreover, we show that this leftward flow may produce asymmetric distribution of exogenously introduced proteins, suggesting morphogen gradients as a subsequent mechanism of left-right axis determination. Finally, we experimentally and theoretically characterize under which conditions a morphogen gradient can arise from the flow.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / physiology*
  • Animals
  • Biological Evolution
  • Blastocyst / physiology
  • Blastocyst / ultrastructure
  • Body Patterning / physiology*
  • Cells, Cultured
  • Cilia / physiology*
  • Cilia / ultrastructure
  • Embryo, Mammalian / embryology*
  • Embryo, Mammalian / ultrastructure
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / ultrastructure
  • Functional Laterality / physiology*
  • Mice
  • Microscopy, Electron, Scanning
  • Oryzias
  • Rabbits
  • Species Specificity