1. Computational and Systems Biology
  2. Physics of Living Systems
Download icon

Persistence, period and precision of autonomous cellular oscillators from the zebrafish segmentation clock

  1. Alexis B Webb
  2. Iván M Lengyel
  3. David J Jörg
  4. Guillaume Valentin
  5. Frank Jülicher
  6. Luis G Morelli
  7. Andrew C Oates  Is a corresponding author
  1. The Francis Crick Institute, United Kingdom
  2. CONICET, Argentina
  3. Max Planck Institute for the Physics of Complex Systems, Germany
  4. Genoway, France
Short Report
  • Cited 41
  • Views 3,297
  • Annotations
Cite this article as: eLife 2016;5:e08438 doi: 10.7554/eLife.08438

Abstract

In vertebrate development, the sequential and rhythmic segmentation of the body axis is regulated by a 'segmentation clock.' This clock is comprised of a population of coordinated oscillating cells that together produce rhythmic gene expression patterns in the embryo. Whether individual cells autonomously maintain oscillations, or whether oscillations depend on signals from neighboring cells is unknown. Using a transgenic zebrafish reporter line for the cyclic transcription factor Her1, we recorded single tailbud cells in vitro. We demonstrate that individual cells can behave as autonomous cellular oscillators. We described the observed variability in cell behavior using a theory of generic oscillators with correlated noise. Single cells have longer periods and lower precision than the tissue, highlighting the role of collective processes in the segmentation clock. Our work reveals a population of cells from the zebrafish segmentation clock that behave as self-sustained, autonomous oscillators with distinctive noisy dynamics.

Article and author information

Author details

  1. Alexis B Webb

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    No competing interests declared.
  2. Iván M Lengyel

    Departamento de Física, FCEyN UBA and IFIBA, CONICET, Buenos Aires, Argentina
    Competing interests
    No competing interests declared.
  3. David J Jörg

    Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    Competing interests
    No competing interests declared.
  4. Guillaume Valentin

    Genoway, Lyon, France
    Competing interests
    No competing interests declared.
  5. Frank Jülicher

    Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    Competing interests
    Frank Jülicher, Reviewing editor, eLife.
  6. Luis G Morelli

    Departamento de Física, FCEyN UBA and IFIBA, CONICET, Buenos Aires, Argentina
    Competing interests
    No competing interests declared.
  7. Andrew C Oates

    Mill Hill Laboratory, The Francis Crick Institute, London, United Kingdom
    For correspondence
    andrew.oates@crick.ac.uk
    Competing interests
    No competing interests declared.

Ethics

Animal experimentation: Zebrafish experimentation was carried out in strict accordance with the ethics and regulations of the Saxonian Ministry of the Environment and Agriculture in Germany under licence Az. 74-9165.40-9-2001, and the Home Office in the United Kingdom under project licence PPL No. 70/7675.

Reviewing Editor

  1. Tanya T Whitfield, University of Sheffield, United Kingdom

Publication history

  1. Received: July 8, 2015
  2. Accepted: February 11, 2016
  3. Accepted Manuscript published: February 13, 2016 (version 1)
  4. Version of Record published: March 4, 2016 (version 2)

Copyright

© 2016, Webb 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.

Metrics

  • 3,297
    Page views
  • 832
    Downloads
  • 41
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

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)

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

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

Further reading

    1. Biochemistry and Chemical Biology
    2. Computational and Systems Biology
    Xiaochuan Zhao et al.
    Research Article Updated

    The DNA-binding protein H-NS is a pleiotropic gene regulator in gram-negative bacteria. Through its capacity to sense temperature and other environmental factors, H-NS allows pathogens like Salmonella to adapt their gene expression to their presence inside or outside warm-blooded hosts. To investigate how this sensing mechanism may have evolved to fit different bacterial lifestyles, we compared H-NS orthologs from bacteria that infect humans, plants, and insects, and from bacteria that live on a deep-sea hypothermal vent. The combination of biophysical characterization, high-resolution proton-less nuclear magnetic resonance spectroscopy, and molecular simulations revealed, at an atomistic level, how the same general mechanism was adapted to specific habitats and lifestyles. In particular, we demonstrate how environment-sensing characteristics arise from specifically positioned intra- or intermolecular electrostatic interactions. Our integrative approach clarified the exact modus operandi for H-NS-mediated environmental sensing and suggested that this sensing mechanism resulted from the exaptation of an ancestral protein feature.

    1. Computational and Systems Biology
    2. Genetics and Genomics
    Reza K Hammond et al.
    Research Article Updated

    To uncover novel significant association signals (p<5×10−8), genome-wide association studies (GWAS) requires increasingly larger sample sizes to overcome statistical correction for multiple testing. As an alternative, we aimed to identify associations among suggestive signals (5 × 10−8≤p<5×10−4) in increasingly powered GWAS efforts using chromatin accessibility and direct contact with gene promoters as biological constraints. We conducted retrospective analyses of three GIANT BMI GWAS efforts using ATAC-seq and promoter-focused Capture C data from human adipocytes and embryonic stem cell (ESC)-derived hypothalamic-like neurons. This approach, with its extremely low false-positive rate, identified 15 loci at p<5×10−5 in the 2010 GWAS, of which 13 achieved genome-wide significance by 2018, including at NAV1, MTIF3, and ADCY3. Eighty percent of constrained 2015 loci achieved genome-wide significance in 2018. We observed similar results in waist-to-hip ratio analyses. In conclusion, biological constraints on sub-significant GWAS signals can reveal potentially true-positive loci for further investigation in existing data sets without increasing sample size.