title: A gene regulatory motif that generates oscillatory or multiway switch outputs.
abstract: 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.
authors.affiliation: Social and Mathematical Epidemiology Group, London School of Hygiene and Tropical Medicine, Faculty of Public Health and Policy, 15-17 Tavistock Place, London, UK.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Panovska-Griffiths
authors.forename: Karen M
authors.initials: KM
authors.lastname: Page
authors.forename: James
authors.initials: J
authors.lastname: Briscoe
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics*; D053823:Hedgehog Proteins / Q000378:metabolism*; D008954:Models, Biological; D054259:Neural Tube / Q000196:embryology* / Q000378:metabolism; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism*; D014714:Vertebrates / Q000196:embryology*
chemical_list: D053823:Hedgehog Proteins; D014157:Transcription Factors