Differential adhesion regulates neurite placement via a retrograde zippering mechanism

  1. Titas Sengupta
  2. Noelle L Koonce
  3. Nabor Vázquez-Martínez
  4. Mark W Moyle
  5. Leighton H Duncan
  6. Sarah E Emerson
  7. Xiaofei Han
  8. Lin Shao
  9. Yicong Wu
  10. Anthony Santella
  11. Li Fan
  12. Zhirong Bao
  13. William Mohler
  14. Hari Shroff
  15. Daniel A Colón-Ramos  Is a corresponding author
  1. Yale University School of Medicine, United States
  2. National Institutes of Health, United States
  3. Sloan-Kettering Institute, United States
  4. Weill Cornell Medicine, United States
  5. University of Connecticut Health Center, United States

Abstract

During development, neurites and synapses segregate into specific neighborhoods or layers within nerve bundles. The developmental programs guiding placement of neurites in specific layers, and hence their incorporation into specific circuits, are not well understood. We implement novel imaging methods and quantitative models to document the embryonic development of the C. elegans brain neuropil, and discover that differential adhesion mechanisms control precise placement of single neurites onto specific layers. Differential adhesion is orchestrated via developmentally-regulated expression of the IgCAM SYG-1, and its partner ligand SYG-2. Changes in SYG-1 expression across neuropil layers result in changes in adhesive forces, which sort SYG-2-expressing neurons. Sorting to layers occurs, not via outgrowth from the neurite tip, but via an alternate mechanism of retrograde zippering, involving interactions between neurite shafts. Our study indicates that biophysical principles from differential adhesion govern neurite placement and synaptic specificity in vivo in developing neuropil bundles.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all plots in which individual data points are not represented - Figure 4N, Figure 6K, Figure 1-figure supplement 2I, Figure 1-figure supplement 2J, Figure 5-figure supplement 4N, Figure 6-figure supplement 1C, Figure 7-figure supplement 3N

Article and author information

Author details

  1. Titas Sengupta

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7228-719X
  2. Noelle L Koonce

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nabor Vázquez-Martínez

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Mark W Moyle

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Leighton H Duncan

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Sarah E Emerson

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Xiaofei Han

    National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Lin Shao

    Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Yicong Wu

    National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Anthony Santella

    Developmental Biology Program, Molecular Cytology Core, Sloan-Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Li Fan

    Helen and Robert Appel Alzheimer's Disease Institute, Weill Cornell Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Zhirong Bao

    Developmental Biology Program, Sloan-Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2201-2745
  13. William Mohler

    Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Hari Shroff

    National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Daniel A Colón-Ramos

    Yale University School of Medicine, New Haven, United States
    For correspondence
    daniel.colon-ramos@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0223-7717

Funding

National Institutes of Health (R24-OD01647)

  • Zhirong Bao
  • William Mohler
  • Daniel A Colón-Ramos

National Institutes of Health (NIBIB Intramural Research Program)

  • Hari Shroff

National Institutes of Health (P30CA008748)

  • Zhirong Bao

National Institutes of Health (R01NS076558)

  • Daniel A Colón-Ramos

National Institutes of Health (DP1NS111778)

  • Daniel A Colón-Ramos

Howard Hughes Medical Institute (Faculty Scholar Award)

  • Daniel A Colón-Ramos

Marine Biological Laboratory (Whitman and Fellows program)

  • Hari Shroff
  • Daniel A Colón-Ramos

Gordon and Betty Moore Foundation (Moore Grant)

  • Hari Shroff
  • Daniel A Colón-Ramos

Gruber Foundation (Gruber Science Fellowship)

  • Titas Sengupta

National Institutes of Health (Predoctoral Training Program in Genetics NIH 2020 T32 GM.)

  • Noelle L Koonce

National Institutes of Health (F32-NS098616)

  • Mark W Moyle

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

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Version history

  1. Received: June 11, 2021
  2. Accepted: November 15, 2021
  3. Accepted Manuscript published: November 16, 2021 (version 1)
  4. Version of Record published: February 10, 2022 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Titas Sengupta
  2. Noelle L Koonce
  3. Nabor Vázquez-Martínez
  4. Mark W Moyle
  5. Leighton H Duncan
  6. Sarah E Emerson
  7. Xiaofei Han
  8. Lin Shao
  9. Yicong Wu
  10. Anthony Santella
  11. Li Fan
  12. Zhirong Bao
  13. William Mohler
  14. Hari Shroff
  15. Daniel A Colón-Ramos
(2021)
Differential adhesion regulates neurite placement via a retrograde zippering mechanism
eLife 10:e71171.
https://doi.org/10.7554/eLife.71171

Share this article

https://doi.org/10.7554/eLife.71171

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