1. Developmental Biology
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The Wg and Dpp morphogens regulate gene expression by modulating the frequency of transcriptional bursts

  1. Rachael Bakker
  2. Madhav Mani  Is a corresponding author
  3. Richard W Carthew  Is a corresponding author
  1. Northwestern University, United States
Research Article
  • Cited 4
  • Views 1,453
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Cite this article as: eLife 2020;9:e56076 doi: 10.7554/eLife.56076

Abstract

Morphogen signaling contributes to the patterned spatiotemporal expression of genes during development. One mode of regulation of signaling-responsive genes is at the level of transcription. Single-cell quantitative studies of transcription have revealed that transcription occurs intermittently, in bursts. Although the effects of many gene regulatory mechanisms on transcriptional bursting have been studied, it remains unclear how morphogen gradients affect this dynamic property of downstream genes. Here we have adapted single molecule fluorescence in situ hybridization (smFISH) for use in the Drosophila wing imaginal disc in order to measure nascent and mature mRNA of genes downstream of the Wg and Dpp morphogen gradients. We compared our experimental results with predictions from stochastic models of transcription, which indicated that the transcription levels of these genes appear to share a common method of control via burst frequency modulation. Our data helps further elucidate the link between developmental gene regulatory mechanisms and transcriptional bursting.

Data availability

All smFISH data after image segmentation have been deposited in the Public Data Repository at Northwestern University's Library. These data are freely available at https://doi.org/10.21985/n2-rfax-bk36 There are no restrictions.

The following data sets were generated
    1. Bakker R
    2. Mani M
    3. Carthew RW
    (2020) Data related to Bakker et al 2020 eLife paper
    Northwestern University Library Data Repository, doi.org/10.21985/n2-rfax-bk36.

Article and author information

Author details

  1. Rachael Bakker

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Madhav Mani

    Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, United States
    For correspondence
    madhav.mani@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
  3. Richard W Carthew

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    For correspondence
    r-carthew@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0343-0156

Funding

National Institutes of Health (R35GM118144)

  • Richard W Carthew

National Institutes of Health (T32CA080621)

  • Rachael Bakker

National Science Foundation (1764421)

  • Madhav Mani
  • Richard W Carthew

Simons Foundation (597491)

  • Madhav Mani
  • Richard W Carthew

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Hugo J Bellen, Baylor College of Medicine, United States

Publication history

  1. Received: February 16, 2020
  2. Accepted: June 18, 2020
  3. Accepted Manuscript published: June 22, 2020 (version 1)
  4. Version of Record published: July 7, 2020 (version 2)

Copyright

© 2020, Bakker et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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    1. Developmental Biology
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    Research Article Updated

    Spatial boundaries formed during animal development originate from the pre-patterning of tissues by signaling molecules, called morphogens. The accuracy of boundary location is limited by the fluctuations of morphogen concentration that thresholds the expression level of target gene. Producing more morphogen molecules, which gives rise to smaller relative fluctuations, would better serve to shape more precise target boundaries; however, it incurs more thermodynamic cost. In the classical diffusion-depletion model of morphogen profile formation, the morphogen molecules synthesized from a local source display an exponentially decaying concentration profile with a characteristic length λ. Our theory suggests that in order to attain a precise profile with the minimal cost, λ should be roughly half the distance to the target boundary position from the source. Remarkably, we find that the profiles of morphogens that pattern the Drosophila embryo and wing imaginal disk are formed with nearly optimal λ. Our finding underscores the cost-effectiveness of precise morphogen profile formation in Drosophila development.