 Spatial Bistability Generates hunchback Expression Sharpness in the Drosophila EmbryoFrancisco J P Lopes, Fernando M C Vieira, David M Holloway, Paulo M Bisch and Alexander V Spirov PLOS Computational Biology, 2008, vol. 4, issue 9, 1-14 Abstract: During embryonic development, the positional information provided by concentration gradients of maternal factors directs pattern formation by providing spatially dependent cues for gene expression. In the fruit fly, Drosophila melanogaster, a classic example of this is the sharp on–off activation of the hunchback (hb) gene at midembryo, in response to local concentrations of the smooth anterior–posterior Bicoid (Bcd) gradient. The regulatory region for hb contains multiple binding sites for the Bcd protein as well as multiple binding sites for the Hb protein. Some previous studies have suggested that Bcd is sufficient for properly sharpened Hb expression, yet other evidence suggests a need for additional regulation. We experimentally quantified the dynamics of hb gene expression in flies that were wild-type, were mutant for hb self-regulation or Bcd binding, or contained an artificial promoter construct consisting of six Bcd and two Hb sites. In addition to these experiments, we developed a reaction–diffusion model of hb transcription, with Bcd cooperative binding and hb self-regulation, and used Zero Eigenvalue Analysis to look for multiple stationary states in the reaction network. Our model reproduces the hb developmental dynamics and correctly predicts the mutant patterns. Analysis of our model indicates that the Hb sharpness can be produced by spatial bistability, in which hb self-regulation produces two stable levels of expression. In the absence of self-regulation, the bistable behavior vanishes and Hb sharpness is disrupted. Bcd cooperative binding affects the position where bistability occurs but is not itself sufficient for a sharp Hb pattern. Our results show that the control of Hb sharpness and positioning, by hb self-regulation and Bcd cooperativity, respectively, are separate processes that can be altered independently. Our model, which matches the changes in Hb position and sharpness observed in different experiments, provides a theoretical framework for understanding the data and in particular indicates that spatial bistability can play a central role in threshold-dependent reading mechanisms of positional information.Author Summary: Pattern formation during embryonic development, or morphogenesis, is one of the most intriguing problems in biology, entailing the sequence of processes by which a relatively simple system, the fertilized egg, becomes a mature organism. In these processes, the genetic information, stored at the molecular scale in the DNA, is translated into the macroscopic spatial expression patterns that precede the tissue–organ scale of body organization. It can also be understood as a flux of information from the genetic to the organ–system level. In the fruit fly Drosophila melanogaster, one of the early processes during its embryonic development is the formation of the sharp Hunchback protein pattern. To generate this pattern, the hunchback gene interprets the position-dependent information in the shallow maternal Bicoid gradient and converts it into the sharp Hunchback protein pattern. We propose that bistability in the dynamics of hunchback gene regulation can account for this information reading process, and we show that this bistable mechanism can be produced by the ability of this gene to regulate its own expression. The solution of this problem offers new approaches to understand the phenomenon of morphogenesis. Date: 2008 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1000184 DOI: 10.1371/journal.pcbi.1000184 Access Statistics for this article More articles in PLOS Computational Biology from Public Library of Science |
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