1. Cell Biology
  2. Developmental Biology
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Cytoneme delivery of sonic hedgehog from ligand-producing cells requires Myosin 10 and a dispatched-BOC/CDON co-receptor complex

  1. Eric T Hall
  2. Miriam E Dillard
  3. Daniel P Stewart
  4. Yan Zhang
  5. Ben Wagner
  6. Rachel M Levine
  7. Shondra M Pruett-Miller
  8. April Sykes
  9. Jamshid Temirov
  10. Richard E Cheney
  11. Motomi Mori
  12. Camenzind G Robinson
  13. Stacey K Ogden  Is a corresponding author
  1. St. Jude Children's Research Hospital, United States
  2. St Jude Children's Research Hospital, United States
  3. University of North Carolina School of Medicine, United States
Research Article
  • Cited 2
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Cite this article as: eLife 2021;10:e61432 doi: 10.7554/eLife.61432

Abstract

Morphogens function in concentration-dependent manners to instruct cell fate during tissue patterning. The cytoneme morphogen transport model posits that specialized filopodia extend between morphogen-sending and responding cells to ensure that appropriate signaling thresholds are achieved. How morphogens are transported along and deployed from cytonemes, how quickly a cytoneme-delivered, receptor-dependent signal is initiated, and whether these processes are conserved across phyla are not known. Herein, we reveal that the actin motor Myosin 10 promotes vesicular transport of Sonic Hedgehog (SHH) morphogen in mouse cell cytonemes, and that SHH morphogen gradient organization is altered in neural tubes of Myo10-/- mice. We demonstrate that cytoneme-mediated deposition of SHH onto receiving cells induces a rapid, receptor-dependent signal response that occurs within seconds of ligand delivery. This activity is dependent upon a novel Dispatched (DISP)-BOC/CDON co-receptor complex that functions in ligand-producing cells to promote cytoneme occurrence and facilitate ligand delivery for signal activation.

Data availability

All data generated or analyzed during the study are included in the manuscript and supporting files. Source files are provided for Figure 2.

Article and author information

Author details

  1. Eric T Hall

    Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Miriam E Dillard

    Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Daniel P Stewart

    Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yan Zhang

    Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ben Wagner

    Cellular Imaging, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Rachel M Levine

    Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Shondra M Pruett-Miller

    Department of Cell and Molecular Biology, St Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3793-585X
  8. April Sykes

    Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jamshid Temirov

    Cell and Molecular Biology, St. Jude Children's Research Hospital, memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Richard E Cheney

    Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Motomi Mori

    Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Camenzind G Robinson

    Cell and Tissue Imaging, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7277-692X
  13. Stacey K Ogden

    Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, United States
    For correspondence
    stacey.ogden@stjude.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8991-3065

Funding

National Institute of General Medical Sciences (R35GM122546)

  • Stacey K Ogden

National Institute of General Medical Sciences (R01GM134531)

  • Richard E Cheney

National Cancer Institute (P30 CA021765)

  • Camenzind G Robinson

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

Ethics

Animal experimentation: The study was performed per recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were handled according to the approved institutional animal care and use committee protocol number 608-100616-10/19 of St. Jude Children's Research Hospital. All effort was made to minimize suffering.

Reviewing Editor

  1. Duojia Pan, UT Southwestern Medical Center and HHMI, United States

Publication history

  1. Received: July 25, 2020
  2. Accepted: February 10, 2021
  3. Accepted Manuscript published: February 11, 2021 (version 1)
  4. Version of Record published: March 17, 2021 (version 2)

Copyright

© 2021, Hall 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.

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