Rere controls retinoic acid signalling and somite bilateral symmetry

Nature. 2010 Feb 18;463(7283):953-7. doi: 10.1038/nature08763.


One of the most notable features of the vertebrate body plan organization is its bilateral symmetry, evident at the level of vertebrae and skeletal muscles. Here we show that a mutation in Rere (also known as atrophin2) leads to the formation of asymmetrical somites in mouse embryos, similar to embryos deprived of retinoic acid. Furthermore, we also demonstrate that Rere controls retinoic acid signalling, which is required to maintain somite symmetry by interacting with Fgf8 in the left-right signalling pathway. Rere forms a complex with Nr2f2, p300 (also known as Ep300) and a retinoic acid receptor, which is recruited to the retinoic acid regulatory element of retinoic acid targets, such as the Rarb promoter. Furthermore, the knockdown of Nr2f2 and/or Rere decreases retinoic acid signalling, suggesting that this complex is required to promote transcriptional activation of retinoic acid targets. The asymmetrical expression of Nr2f2 in the presomitic mesoderm overlaps with the asymmetry of the retinoic acid signalling response, supporting its implication in the control of somitic symmetry. Misregulation of this mechanism could be involved in symmetry defects of the human spine, such as those observed in patients with scoliosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / physiology*
  • COUP Transcription Factor II / deficiency
  • COUP Transcription Factor II / genetics
  • COUP Transcription Factor II / metabolism
  • Cell Line
  • E1A-Associated p300 Protein / metabolism
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Fibroblast Growth Factor 8 / metabolism
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Inbred C57BL
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Promoter Regions, Genetic / genetics
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Repressor Proteins / deficiency
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Response Elements / genetics
  • Signal Transduction*
  • Somites / embryology*
  • Somites / metabolism*
  • Tretinoin / metabolism*


  • COUP Transcription Factor II
  • Fgf8 protein, mouse
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Nr2f2 protein, mouse
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • atrophin 2, mouse
  • retinoic acid receptor beta
  • Fibroblast Growth Factor 8
  • Tretinoin
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse