Pitx2 determines left-right asymmetry of internal organs in vertebrates

Nature. 1998 Aug 6;394(6693):545-51. doi: 10.1038/29004.


The handedness of visceral organs is conserved among vertebrates and is regulated by asymmetric signals relayed by molecules such as Shh, Nodal and activin. The gene Pitx2 is expressed in the left lateral plate mesoderm and, subsequently, in the left heart and gut of mouse, chick and Xenopus embryos. Misexpression of Shh and Nodal induces Pitx2 expression, whereas inhibition of activin signalling blocks it. Misexpression of Pitx2 alters the relative position of organs and the direction of body rotation in chick and Xenopus embryos. Changes in Pitx2 expression are evident in mouse mutants with laterality defects. Thus, Pitx2 seems to serve as a critical downstream transcription target that mediates left-right asymmetry in vertebrates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors, Type II
  • Animals
  • Body Patterning / physiology*
  • Chick Embryo
  • Culture Techniques
  • Hedgehog Proteins
  • Homeodomain Proteins / physiology*
  • Mice
  • Molecular Sequence Data
  • Nodal Protein
  • Nuclear Proteins*
  • Paired Box Transcription Factors
  • Proteins / physiology
  • Receptors, Growth Factor / physiology
  • Situs Inversus / embryology
  • Trans-Activators*
  • Transcription Factors / physiology*
  • Transforming Growth Factor beta*
  • Xenopus


  • Hedgehog Proteins
  • Homeodomain Proteins
  • Nodal Protein
  • Nodal protein, mouse
  • Nuclear Proteins
  • Paired Box Transcription Factors
  • Proteins
  • Receptors, Growth Factor
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • homeobox protein PITX1
  • homeobox protein PITX3
  • homeobox protein PITX2
  • Activin Receptors, Type II

Associated data

  • GENBANK/AF077092
  • GENBANK/AF077767