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

2015; Nature Portfolio; Volume: 16; Issue: 2 Linguagem: Inglês

10.1038/nrm3932

1471-0080

Thomas J. Cunningham, Gregg Duester,

Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Retinoic acid regulates transcription by interacting with nuclear retinoic acid receptors, which bind to retinoic acid response elements near target genes. Recent studies have refined our knowledge of retinoic acid function in the limb, which serves as a paradigm for understanding how it regulates other developmental processes, such as somitogenesis, neuronal differentiation and organogenesis. 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.