Function of Rieger syndrome gene in left-right asymmetry and craniofacial development

Nature. 1999 Sep 16;401(6750):276-8. doi: 10.1038/45797.


Rieger syndrome, an autosomal dominant disorder, includes ocular, craniofacial and umbilical abnormalities. The pitx2 homeobox gene, which is mutated in Rieger syndrome, has been proposed to be the effector molecule interpreting left-right axial information from the early embryonic trunk to each organ. Here we have used gene targeting in mice to generate a loss-of-function allele that would be predicted to result in organ randomization or isomerization. Although pitx2-/- embryos had abnormal cardiac morphogenesis, mutant hearts looped in the normal direction. Pitx2-/- embryos had correctly oriented, but arrested, embryonic rotation and right pulmonary isomerism. They also had defective development of the mandibular and maxillary facial prominences, regression of the stomodeum and arrested tooth development. Fgf8 expression was absent, and Bmp4 expression was expanded in the branchial-arch ectoderm. These data reveal a critical role for pitx2 in left-right asymmetry but indicate that pitx2 may function at an intermediate step in cardiac morphogenesis and embryonic rotation.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / embryology
  • Abnormalities, Multiple / genetics*
  • Alleles
  • Animals
  • Body Patterning / genetics*
  • Craniofacial Abnormalities / embryology
  • Craniofacial Abnormalities / genetics*
  • Gene Targeting
  • Heart / embryology
  • Heart Defects, Congenital / embryology
  • Heart Defects, Congenital / genetics
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / physiology
  • Lung / abnormalities
  • Lung / embryology
  • Mice
  • Mutation
  • Nuclear Proteins*
  • Paired Box Transcription Factors
  • Syndrome
  • Transcription Factors / genetics*
  • Transcription Factors / physiology


  • Homeodomain Proteins
  • Nuclear Proteins
  • Paired Box Transcription Factors
  • Transcription Factors
  • homeobox protein PITX1
  • homeobox protein PITX3
  • homeobox protein PITX2