Deconstruction of the Beaten Path-Sidestep interaction network provides insights into neuromuscular system development

  1. Hanqing Li
  2. Ash Watson
  3. Agnieszka Olechwier
  4. Michael Anaya
  5. Siamak K Sorooshyari
  6. Dermott P Harnett
  7. Hyung-Kook (Peter) Lee
  8. Jost Vielmetter
  9. Mario A Fares
  10. K Christopher Garcia
  11. Engin Özkan
  12. Juan-Pablo Labrador
  13. Kai Zinn  Is a corresponding author
  1. California Institute of Technology, United States
  2. Trinity College Dublin, Ireland
  3. University of Chicago, United States
  4. Ellipsis Health, United States
  5. Howard Hughes Medical Institute, Stanford University School of Medicine, United States

Abstract

An "interactome" screen of all Drosophila cell-surface and secreted proteins containing immunoglobulin superfamily (IgSF) domains discovered a network formed by paralogs of Beaten Path (Beat) and Sidestep (Side), a ligand-receptor pair that is central to motor axon guidance. Here we describe a new method for interactome screening, the Bio-Plex Interactome Assay (BPIA), which allows identification of many interactions in a single sample. Using the BPIA, we "deorphanized" four more members of the Beat-Side network. We confirmed interactions using surface plasmon resonance. The expression patterns of beat and side genes suggest that Beats are neuronal receptors for Sides expressed on peripheral tissues. side-VI is expressed in muscle fibers targeted by the ISNb nerve, as well as at growth cone choice points and synaptic targets for the ISN and TN nerves. beat-V genes, encoding Side-VI receptors, are expressed in ISNb and ISN motor neurons.

Article and author information

Author details

  1. Hanqing Li

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ash Watson

    Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  3. Agnieszka Olechwier

    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael Anaya

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Siamak K Sorooshyari

    Ellipsis Health, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1172-6291
  6. Dermott P Harnett

    Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  7. Hyung-Kook (Peter) Lee

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jost Vielmetter

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Mario A Fares

    Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  10. K Christopher Garcia

    Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9273-0278
  11. Engin Özkan

    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0263-6729
  12. Juan-Pablo Labrador

    Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  13. Kai Zinn

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    zinnk@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6706-5605

Funding

NIH (R37)

  • Kai Zinn

SFI

  • Juan-Pablo Labrador

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

Copyright

© 2017, Li 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

  • 3,876
    views
  • 614
    downloads
  • 47
    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. Hanqing Li
  2. Ash Watson
  3. Agnieszka Olechwier
  4. Michael Anaya
  5. Siamak K Sorooshyari
  6. Dermott P Harnett
  7. Hyung-Kook (Peter) Lee
  8. Jost Vielmetter
  9. Mario A Fares
  10. K Christopher Garcia
  11. Engin Özkan
  12. Juan-Pablo Labrador
  13. Kai Zinn
(2017)
Deconstruction of the Beaten Path-Sidestep interaction network provides insights into neuromuscular system development
eLife 6:e28111.
https://doi.org/10.7554/eLife.28111

Share this article

https://doi.org/10.7554/eLife.28111

Further reading

    1. Neuroscience
    Franziska Auer, Katherine Nardone ... David Schoppik
    Research Article

    Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.

    1. Neuroscience
    Zhujun Shao, Mengya Zhang, Qing Yu
    Research Article

    When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.