1. Computational and Systems Biology
  2. Developmental Biology
Download icon

Dynamics of BMP signaling and distribution during zebrafish dorsal-ventral patterning

  1. Autumn P Pomreinke
  2. Gary H Soh
  3. Katherine W Rogers
  4. Jennifer K Bergmann
  5. Alexander J Bläßle
  6. Patrick Müller  Is a corresponding author
  1. Friedrich Miescher Laboratory of the Max Planck Society, Germany
Research Article
  • Cited 25
  • Views 2,745
  • Annotations
Cite this article as: eLife 2017;6:e25861 doi: 10.7554/eLife.25861

Abstract

During vertebrate embryogenesis, dorsal-ventral patterning is controlled by the BMP/Chordin activator/inhibitor system. BMP induces ventral fates, whereas Chordin inhibits BMP signaling on the dorsal side. Several theories can explain how the distributions of BMP and Chordin are regulated to achieve patterning, but the assumptions regarding activator/inhibitor diffusion and stability differ between models. Notably, “shuttling” models in which the BMP distribution is modulated by a Chordin-mediated increase in BMP diffusivity have gained recent prominence. Here, we directly test five major models by measuring the biophysical properties of fluorescently tagged BMP2b and Chordin in zebrafish embryos. We found that BMP2b and Chordin diffuse and rapidly form extracellular protein gradients, Chordin does not modulate the diffusivity or distribution of BMP2b, and Chordin is not required to establish peak levels of BMP signaling. Our findings challenge current self-regulating reaction-diffusion and shuttling models and provide support for a graded source-sink mechanism underlying zebrafish dorsal-ventral patterning.

Article and author information

Author details

  1. Autumn P Pomreinke

    Systems Biology of Development Group, Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Gary H Soh

    Systems Biology of Development Group, Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Katherine W Rogers

    Systems Biology of Development Group, Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5700-2662
  4. Jennifer K Bergmann

    Systems Biology of Development Group, Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Alexander J Bläßle

    Systems Biology of Development Group, Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Patrick Müller

    Systems Biology of Development Group, Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany
    For correspondence
    pmueller@tuebingen.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0702-6209

Funding

Max-Planck-Gesellschaft

  • Patrick Müller

Human Frontier Science Program (Career Development Award CDA00031/2013-C)

  • Patrick Müller

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

Reviewing Editor

  1. Deborah Yelon, University of California, San Diego, United States

Publication history

  1. Received: February 8, 2017
  2. Accepted: August 30, 2017
  3. Accepted Manuscript published: August 31, 2017 (version 1)
  4. Version of Record published: October 26, 2017 (version 2)

Copyright

© 2017, Pomreinke 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

  • 2,745
    Page views
  • 483
    Downloads
  • 25
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, 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. Cell Biology
    2. Computational and Systems Biology
    Peter Jan Hooikaas et al.
    Research Article Updated

    When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome toward the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of microtubule dynamics contributes to this process. Here, we show that the knockout of KIF21B, a kinesin-4 linked to autoimmune disorders, causes microtubule overgrowth and perturbs centrosome translocation. KIF21B restricts microtubule length by inducing microtubule pausing typically followed by catastrophe. Catastrophe induction with vinblastine prevented microtubule overgrowth and was sufficient to rescue centrosome polarization in KIF21B-knockout cells. Biophysical simulations showed that a relatively small number of KIF21B molecules can restrict mirotubule length and promote an imbalance of dynein-mediated pulling forces that allows the centrosome to translocate past the nucleus. We conclude that proper control of microtubule length is important for allowing rapid remodeling of the cytoskeleton and efficient T cell polarization.

    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.