Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system

Dev Cell. 2006 Oct;11(4):495-504. doi: 10.1016/j.devcel.2006.08.002.

Abstract

The bilateral symmetry of the mouse embryo is broken by leftward fluid flow in the node. However, it is unclear how this directional flow is then translated into the robust, left side-specific Nodal gene expression that determines and coordinates left-right situs throughout the embryo. While manipulating Nodal and Lefty gene expression, we have observed phenomena that are indicative of the involvement of a self-enhancement and lateral-inhibition (SELI) system. We constructed a mathematical SELI model that not only simulates, but also predicts, experimental data. As predicted by the model, Nodal expression initiates even on the right side. These results indicate that directional flow represents an initial small difference between the left and right sides of the embryo, but is insufficient to determine embryonic situs. Nodal and Lefty are deployed as a SELI system required to amplify this initial bias and convert it into robust asymmetry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Body Patterning / physiology*
  • Computer Simulation
  • Embryo, Mammalian / embryology*
  • Embryonic Induction*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Genetic Vectors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • In Situ Hybridization
  • Left-Right Determination Factors
  • Mice
  • Mice, Mutant Strains
  • Models, Biological
  • Models, Theoretical
  • Nodal Protein
  • Organ Culture Techniques
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • Forkhead Transcription Factors
  • Foxh1 protein, mouse
  • Homeodomain Proteins
  • Left-Right Determination Factors
  • Nodal Protein
  • Nodal protein, mouse
  • Transcription Factors
  • Transforming Growth Factor beta
  • homeobox protein PITX2