Physical limits of flow sensing in the left-right organizer

  1. Rita R Ferreira
  2. Andrej Vilfan  Is a corresponding author
  3. Frank Jülicher
  4. Willy Supatto  Is a corresponding author
  5. Julien Vermot  Is a corresponding author
  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, France
  2. J. Stefan Institute, Slovenia
  3. Max-Planck-Institute for the Physics of Complex Systems, Germany
  4. Ecole Polytechnique, Centre National de la Recherche Scientifique (UMR7645), France

Abstract

Fluid flows generated by motile cilia are guiding the establishment of the left-right asymmetry of the body in the vertebrate left-right organizer. Competing hypotheses have been proposed: the direction of flow is sensed either through mechanosensation, or via the detection of chemical signals transported in the flow. We investigated the physical limits of flow detection in order to clarify which mechanisms could be reliably used for symmetry breaking. We integrated parameters describing cilia distribution and orientation obtained in vivo in zebrafish into a multiscale physical study of flow generation and detection. Our results show that the number of immotile cilia is too small to ensure robust left and right determination by mechanosensing, given the large spatial variability of the flow. However, motile cilia could sense their own motion by a yet unknown mechanism. Finally, transport of chemical signals by the flow can provide a simple and reliable mechanism of asymmetry establishment.

Article and author information

Author details

  1. Rita R Ferreira

    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
    Competing interests
    No competing interests declared.
  2. Andrej Vilfan

    J. Stefan Institute, Ljubljana, Slovenia
    For correspondence
    andrej.vilfan@ijs.si
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8985-6072
  3. Frank Jülicher

    Max-Planck-Institute for the Physics of Complex Systems, Dresden, Germany
    Competing interests
    Frank Jülicher, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4731-9185
  4. Willy Supatto

    Laboratory for Optics and Biosciences, Ecole Polytechnique, Centre National de la Recherche Scientifique (UMR7645), Palaiseau, France
    For correspondence
    willy.supatto@polytechnique.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4562-9166
  5. Julien Vermot

    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
    For correspondence
    julien@igbmc.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8924-732X

Funding

Human Frontier Science Program (CDA00032/2010-C)

  • Julien Vermot

Labex (ANR-10-LABX-0030-INRT)

  • Rita R Ferreira
  • Julien Vermot

Agence Nationale de la Recherche (ANR-13-BSV1-0016)

  • Julien Vermot

Agence Nationale de la Recherche (ANR- 12-ISV2-0001)

  • Julien Vermot

Agence Nationale de la Recherche (ANR-2010-JCJC-1510-01​)

  • Willy Supatto

Agence Nationale de la Recherche (ANR-11-EQPX-0029​)

  • Willy Supatto

Javna Agencija za Raziskovalno Dejavnost RS (grant J1-5437)

  • Andrej Vilfan

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

Reviewing Editor

  1. Richard M Berry, University of Oxford, United Kingdom

Ethics

Animal experimentation: Animal experiments were approved by the Animal Experimentation Committee of the Institutional Review Board of the IGBMC.

Version history

  1. Received: January 19, 2017
  2. Accepted: June 13, 2017
  3. Accepted Manuscript published: June 14, 2017 (version 1)
  4. Version of Record published: August 4, 2017 (version 2)

Copyright

© 2017, Ferreira 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

  • 3,317
    views
  • 647
    downloads
  • 45
    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. Rita R Ferreira
  2. Andrej Vilfan
  3. Frank Jülicher
  4. Willy Supatto
  5. Julien Vermot
(2017)
Physical limits of flow sensing in the left-right organizer
eLife 6:e25078.
https://doi.org/10.7554/eLife.25078

Share this article

https://doi.org/10.7554/eLife.25078

Further reading

    1. Computational and Systems Biology
    Maksim Kleverov, Daria Zenkova ... Alexey A Sergushichev
    Research Article

    Transcriptomic profiling became a standard approach to quantify a cell state, which led to accumulation of huge amount of public gene expression datasets. However, both reuse of these datasets or analysis of newly generated ones requires significant technical expertise. Here we present Phantasus - a user-friendly web-application for interactive gene expression analysis which provides a streamlined access to more than 96000 public gene expression datasets, as well as allows analysis of user-uploaded datasets. Phantasus integrates an intuitive and highly interactive JavaScript-based heatmap interface with an ability to run sophisticated R-based analysis methods. Overall Phantasus allows users to go all the way from loading, normalizing and filtering data to doing differential gene expression and downstream analysis. Phantasus can be accessed on-line at https://alserglab.wustl.edu/phantasus or can be installed locally from Bioconductor (https://bioconductor.org/packages/phantasus). Phantasus source code is available at https://github.com/ctlab/phantasus under MIT license.

    1. Computational and Systems Biology
    2. Evolutionary Biology
    Ryan T Bell, Harutyun Sahakyan ... Eugene V Koonin
    Research Article

    A comprehensive census of McrBC systems, among the most common forms of prokaryotic Type IV restriction systems, followed by phylogenetic analysis, reveals their enormous abundance in diverse prokaryotes and a plethora of genomic associations. We focus on a previously uncharacterized branch, which we denote coiled-coil nuclease tandems (CoCoNuTs) for their salient features: the presence of extensive coiled-coil structures and tandem nucleases. The CoCoNuTs alone show extraordinary variety, with three distinct types and multiple subtypes. All CoCoNuTs contain domains predicted to interact with translation system components, such as OB-folds resembling the SmpB protein that binds bacterial transfer-messenger RNA (tmRNA), YTH-like domains that might recognize methylated tmRNA, tRNA, or rRNA, and RNA-binding Hsp70 chaperone homologs, along with RNases, such as HEPN domains, all suggesting that the CoCoNuTs target RNA. Many CoCoNuTs might additionally target DNA, via McrC nuclease homologs. Additional restriction systems, such as Type I RM, BREX, and Druantia Type III, are frequently encoded in the same predicted superoperons. In many of these superoperons, CoCoNuTs are likely regulated by cyclic nucleotides, possibly, RNA fragments with cyclic termini, that bind associated CARF (CRISPR-Associated Rossmann Fold) domains. We hypothesize that the CoCoNuTs, together with the ancillary restriction factors, employ an echeloned defense strategy analogous to that of Type III CRISPR-Cas systems, in which an immune response eliminating virus DNA and/or RNA is launched first, but then, if it fails, an abortive infection response leading to PCD/dormancy via host RNA cleavage takes over.