Odd-paired controls frequency doubling in Drosophila segmentation by altering the pair-rule gene regulatory network

  1. Erik Clark  Is a corresponding author
  2. Michael Akam
  1. University of Cambridge, United Kingdom

Abstract

The Drosophila embryo transiently exhibits a double segment periodicity, defined by the expression of seven "pair-rule" genes, each in a pattern of seven stripes. At gastrulation, interactions between the pair-rule genes lead to frequency doubling and the patterning of fourteen parasegment boundaries. In contrast to earlier stages of Drosophila anteroposterior patterning, this transition is not well understood. By carefully analysing the spatiotemporal dynamics of pair-rule gene expression, we demonstrate that frequency-doubling is precipitated by multiple coordinated changes to the network of regulatory interactions between the pair-rule genes. We identify the broadly expressed but temporally patterned transcription factor, Odd-paired (Opa/Zic), as the cause of these changes, and show that the patterning of the even-numbered parasegment boundaries relies on Opa-dependent regulatory interactions. Our findings indicate that the pair-rule gene regulatory network has a temporally-modulated topology, permitting the pair-rule genes to play stage-specific patterning roles.

Data availability

The following data sets were generated

Article and author information

Author details

  1. Erik Clark

    Laboratory for Development and Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    ec491@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5588-796X
  2. Michael Akam

    Laboratory for Development and Evolution, Department of Zoology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0063-2297

Funding

Biotechnology and Biological Sciences Research Council (PhD Studentship)

  • Erik Clark

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

Copyright

© 2016, Clark & Akam

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.

Metrics

  • 4,623
    views
  • 819
    downloads
  • 64
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Erik Clark
  2. Michael Akam
(2016)
Odd-paired controls frequency doubling in Drosophila segmentation by altering the pair-rule gene regulatory network
eLife 5:e18215.
https://doi.org/10.7554/eLife.18215

Share this article

https://doi.org/10.7554/eLife.18215

Further reading

    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease
    Saugat Poudel, Jason Hyun ... Bernhard O Palsson
    Research Article

    The Staphylococcus aureus clonal complex 8 (CC8) is made up of several subtypes with varying levels of clinical burden; from community-associated methicillin-resistant S. aureus USA300 strains to hospital-associated (HA-MRSA) USA500 strains and ancestral methicillin-susceptible (MSSA) strains. This phenotypic distribution within a single clonal complex makes CC8 an ideal clade to study the emergence of mutations important for antibiotic resistance and community spread. Gene-level analysis comparing USA300 against MSSA and HA-MRSA strains have revealed key horizontally acquired genes important for its rapid spread in the community. However, efforts to define the contributions of point mutations and indels have been confounded by strong linkage disequilibrium resulting from clonal propagation. To break down this confounding effect, we combined genetic association testing with a model of the transcriptional regulatory network (TRN) to find candidate mutations that may have led to changes in gene regulation. First, we used a De Bruijn graph genome-wide association study to enrich mutations unique to the USA300 lineages within CC8. Next, we reconstructed the TRN by using independent component analysis on 670 RNA-sequencing samples from USA300 and non-USA300 CC8 strains which predicted several genes with strain-specific altered expression patterns. Examination of the regulatory region of one of the genes enriched by both approaches, isdH, revealed a 38-bp deletion containing a Fur-binding site and a conserved single-nucleotide polymorphism which likely led to the altered expression levels in USA300 strains. Taken together, our results demonstrate the utility of reconstructed TRNs to address the limits of genetic approaches when studying emerging pathogenic strains.

    1. Computational and Systems Biology
    Masaaki Uematsu, Jeremy M Baskin
    Tools and Resources

    Plasmid construction is central to life science research, and sequence verification is arguably its costliest step. Long-read sequencing has emerged as a competitor to Sanger sequencing, with the principal benefit that whole plasmids can be sequenced in a single run. Nevertheless, the current cost of nanopore sequencing is still prohibitive for routine sequencing during plasmid construction. We develop a computational approach termed Simple Algorithm for Very Efficient Multiplexing of Oxford Nanopore Experiments for You (SAVEMONEY) that guides researchers to mix multiple plasmids and subsequently computationally de-mixes the resultant sequences. SAVEMONEY defines optimal mixtures in a pre-survey step, and following sequencing, executes a post-analysis workflow involving sequence classification, alignment, and consensus determination. By using Bayesian analysis with prior probability of expected plasmid construction error rate, high-confidence sequences can be obtained for each plasmid in the mixture. Plasmids differing by as little as two bases can be mixed as a single sample for nanopore sequencing, and routine multiplexing of even six plasmids per 180 reads can still maintain high accuracy of consensus sequencing. SAVEMONEY should further democratize whole-plasmid sequencing by nanopore and related technologies, driving down the effective cost of whole-plasmid sequencing to lower than that of a single Sanger sequencing run.