Mechanisms of retinoic acid signalling and its roles in organ and limb development

Nat Rev Mol Cell Biol. 2015 Feb;16(2):110-23. doi: 10.1038/nrm3932. Epub 2015 Jan 5.


Retinoic acid (RA) signalling has a central role during vertebrate development. RA synthesized in specific locations regulates transcription by interacting with nuclear RA receptors (RARs) bound to RA response elements (RAREs) near target genes. RA was first implicated in signalling on the basis of its teratogenic effects on limb development. Genetic studies later revealed that endogenous RA promotes forelimb initiation by repressing fibroblast growth factor 8 (Fgf8). Insights into RA function in the limb serve as a paradigm for understanding how RA regulates other developmental processes. In vivo studies have identified RAREs that control repression of Fgf8 during body axis extension or activation of homeobox (Hox) genes and other key regulators during neuronal differentiation and organogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Extremities / growth & development*
  • Fibroblast Growth Factor 8 / genetics
  • Fibroblast Growth Factor 8 / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Signal Transduction / genetics*
  • Tretinoin / metabolism*
  • Vertebrates / genetics
  • Vertebrates / growth & development
  • Vertebrates / metabolism


  • Fibroblast Growth Factor 8
  • Tretinoin