125
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Temporal control of self-organized pattern formation without morphogen gradients in bacteria

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          • Using Escherichia coli programmed by a synthetic gene circuit, we demonstrate the generation of robust, self-organized ring patterns of gene expression in the absence of an apparent morphogen gradient.

          • Instead of being a spatial cue, the morphogen serves as a timing cue to trigger the formation and maintenance of the ring patterns.

          • The timing mechanism enables the system to sense the domain size of the environment and generate patterns that scale accordingly.

          Abstract

          Diverse mechanisms have been proposed to explain biological pattern formation. Regardless of their specific molecular interactions, the majority of these mechanisms require morphogen gradients as the spatial cue, which are either predefined or generated as a part of the patterning process. However, using Escherichia coli programmed by a synthetic gene circuit, we demonstrate here the generation of robust, self-organized ring patterns of gene expression in the absence of an apparent morphogen gradient. Instead of being a spatial cue, the morphogen serves as a timing cue to trigger the formation and maintenance of the ring patterns. The timing mechanism enables the system to sense the domain size of the environment and generate patterns that scale accordingly. Our work defines a novel mechanism of pattern formation that has implications for understanding natural developmental processes.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: not found

          A synthetic multicellular system for programmed pattern formation.

          Pattern formation is a hallmark of coordinated cell behaviour in both single and multicellular organisms. It typically involves cell-cell communication and intracellular signal processing. Here we show a synthetic multicellular system in which genetically engineered 'receiver' cells are programmed to form ring-like patterns of differentiation based on chemical gradients of an acyl-homoserine lactone (AHL) signal that is synthesized by 'sender' cells. In receiver cells, 'band-detect' gene networks respond to user-defined ranges of AHL concentrations. By fusing different fluorescent proteins as outputs of network variants, an initially undifferentiated 'lawn' of receivers is engineered to form a bullseye pattern around a sender colony. Other patterns, such as ellipses and clovers, are achieved by placing senders in different configurations. Experimental and theoretical analyses reveal which kinetic parameters most significantly affect ring development over time. Construction and study of such synthetic multicellular systems can improve our quantitative understanding of naturally occurring developmental processes and may foster applications in tissue engineering, biomaterial fabrication and biosensing.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Growth rate-dependent global effects on gene expression in bacteria.

            Bacterial gene expression depends not only on specific regulatory mechanisms, but also on bacterial growth, because important global parameters such as the abundance of RNA polymerases and ribosomes are all growth-rate dependent. Understanding of these global effects is necessary for a quantitative understanding of gene regulation and for the design of synthetic genetic circuits. We find that the observed growth-rate dependence of constitutive gene expression can be explained by a simple model using the measured growth-rate dependence of the relevant cellular parameters. More complex growth dependencies for genetic circuits involving activators, repressors, and feedback control were analyzed and verified experimentally with synthetic circuits. Additional results suggest a feedback mechanism mediated by general growth-dependent effects that does not require explicit gene regulation if the expressed protein affects cell growth. This mechanism can lead to growth bistability and promote the acquisition of important physiological functions such as antibiotic resistance and tolerance (persistence). Copyright 2009 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Morphogen gradients: from generation to interpretation.

              Morphogens are long-range signaling molecules that pattern developing tissues in a concentration-dependent manner. The graded activity of morphogens within tissues exposes cells to different signal levels and leads to region-specific transcriptional responses and cell fates. In its simplest incarnation, a morphogen signal forms a gradient by diffusion from a local source and clearance in surrounding tissues. Responding cells often transduce morphogen levels in a linear fashion, which results in the graded activation of transcriptional effectors. The concentration-dependent expression of morphogen target genes is achieved by their different binding affinities for transcriptional effectors as well as inputs from other transcriptional regulators. Morphogen distribution and interpretation are the result of complex interactions between the morphogen and responding tissues. The response to a morphogen is dependent not simply on morphogen concentration but also on the duration of morphogen exposure and the state of the target cells. In this review, we describe the morphogen concept and discuss the mechanisms that underlie the generation, modulation, and interpretation of morphogen gradients.
                Bookmark

                Author and article information

                Journal
                Mol Syst Biol
                Mol. Syst. Biol
                Molecular Systems Biology
                Nature Publishing Group
                1744-4292
                2013
                08 October 2013
                08 October 2013
                : 9
                : 697
                Affiliations
                [1 ]Department of Biomedical Engineering, Duke University , Durham, NC, USA
                [2 ]Department of Mathematics, Duke University , Durham, NC, USA
                [3 ]Institute for Genome Sciences and Policy, Duke University , Durham, NC, USA
                [4 ]Duke Center for Systems Biology, Duke University , Durham, NC, USA
                Author notes
                [a ]Department of Biomedical Engineering, Duke University , CIEMAS 2355 101 Science Drive, Box 3382, Durham, NC 27708, USA. Tel.:+1 919 660 8408; Fax:+1 919 668 0795; you@ 123456duke.edu
                [*]

                These authors contributed equally to this work

                Article
                msb201355
                10.1038/msb.2013.55
                3817405
                24104480
                d9623290-86c0-4365-88ac-8f9d7aafa030
                Copyright © 2013, EMBO and Macmillan Publishers Limited

                This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/.

                History
                : 03 April 2013
                : 06 September 2013
                Categories
                Article

                Quantitative & Systems biology
                morphogen,pattern formation,synthetic biology,systems biology,temporal control

                Comments

                Comment on this article