A gene regulatory motif that generates oscillatory or multiway switch outputs

J R Soc Interface. 2012 Dec 12;10(79):20120826. doi: 10.1098/rsif.2012.0826. Print 2013 Feb.


The pattern of gene expression in a developing tissue determines the spatial organization of cell type generation. We previously defined regulatory interactions between a set of transcription factors that specify the pattern of gene expression in progenitors of different neuronal subtypes of the vertebrate neural tube. These transcription factors form a circuit that acts as a multistate switch, patterning the tissue in response to a gradient of Sonic Hedgehog. Here, by simplifying aspects of the regulatory interactions, we found that the topology of the circuit allows either switch-like or oscillatory behaviour depending on parameter values. The qualitative dynamics appear to be controlled by a simpler sub-circuit, which we term the AC-DC motif. We argue that its topology provides a natural way to implement a multistate gene expression switch and we show that the circuit is readily extendable to produce more distinct stripes of gene expression. Our analysis also suggests that AC-DC motifs could be deployed in tissues patterned by oscillatory mechanisms, thus blurring the distinction between pattern-formation mechanisms relying on temporal oscillations or graded signals. Furthermore, during evolution, mechanisms of gradient interpretation might have arisen from oscillatory circuits, or vice versa.

MeSH terms

  • Animals
  • Biological Clocks / physiology
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Regulatory Networks / genetics*
  • Hedgehog Proteins / metabolism*
  • Models, Biological*
  • Neural Tube / embryology*
  • Neural Tube / metabolism
  • Species Specificity
  • Transcription Factors / metabolism*
  • Vertebrates / embryology*


  • Hedgehog Proteins
  • Transcription Factors