1. Developmental Biology
  2. Neuroscience

Tuning of delta-protocadherin adhesion through combinatorial diversity

  1. Adam J Bisogni
  2. Shila Ghazanfar
  3. Eric O Williams
  4. Heather M Marsh
  5. Jean Y H Yang
  6. David M Lin  Is a corresponding author
  1. Cornell University, United States
  2. University of Sydney, Australia
  3. Fitchburg State University, United States
https://doi.org/10.7554/eLife.41050
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  1. Adam J Bisogni
  2. Shila Ghazanfar
  3. Eric O Williams
  4. Heather M Marsh
  5. Jean Y H Yang
  6. David M Lin
(2018)
Tuning of delta-protocadherin adhesion through combinatorial diversity
eLife 7:e41050.
https://doi.org/10.7554/eLife.41050
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Abstract

The delta-protocadherins (δ-Pcdhs) play key roles in neural development, and expression studies suggest they are expressed in combination within neurons. The extent of this combinatorial diversity, and how these combinations influence cell adhesion, is poorly understood. We show that individual mouse olfactory sensory neurons express 0-7 δ-Pcdhs. Despite this apparent combinatorial complexity, K562 cell aggregation assays revealed simple principles mediate tuning of δ-Pcdh adhesion. Cells can vary the number of δ-Pcdhs expressed, the level of surface expression, and which δ-Pcdhs are expressed, as different members possess distinct apparent adhesive affinities. These principles contrast with those identified previously for the clustered protocadherins (cPcdhs), where the particular combination of cPcdhs expressed does not appear to be a critical factor. Despite these differences, we show δ-Pcdhs can modify cPcdh adhesion. Our studies show how intra- and interfamily interactions can greatly amplify the impact of this small subfamily on neuronal function.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. A link to the software code is also provided.

The following previously published data sets were used

Article and author information

Author details

  1. Adam J Bisogni

    Department of Biomedical Sciences, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Shila Ghazanfar

    School of Mathematics and Statistics, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.

  3. Eric O Williams

    Department of Biology and Chemistry, Fitchburg State University, Fitchburg, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Heather M Marsh

    Department of Biomedical Sciences, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Jean Y H Yang

    School of Mathematics and Statistics, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.

  6. David M Lin

    Department of Biomedical Sciences, Cornell University, Ithaca, United States
    For correspondence
    dml45@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9236-8405

Funding

National Institutes of Health (R21DC015107)

  • Adam J Bisogni

Cornell Veterinary College Research Grants Program (Seed Grant)

  • Adam J Bisogni

Australian Research Council (FT0991918)

  • Jean Y H Yang

National Health and Medical Research Council (APP1111338)

  • Jean Y H Yang

Commonwealth Scientific and Industrial Research Organisation (OCE Top Up Scholarship)

  • Shila Ghazanfar

National Institutes of Health (T32HD057854)

  • Adam J Bisogni

Australian Postgraduate Award (Postgraduate Award)

  • Shila Ghazanfar

National Institutes of Health (R01DC007489)

  • Adam J Bisogni
  • Eric O Williams
  • Heather M Marsh

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

Reviewing Editor

  1. Tom Maniatis, Columbia University, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#01-0075) of Cornell University.

Version history

  1. Received: August 17, 2018
  2. Accepted: December 11, 2018
  3. Accepted Manuscript published: December 14, 2018 (version 1)
  4. Version of Record published: January 9, 2019 (version 2)

Copyright

© 2018, Bisogni 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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  1. Adam J Bisogni
  2. Shila Ghazanfar
  3. Eric O Williams
  4. Heather M Marsh
  5. Jean Y H Yang
  6. David M Lin
(2018)
Tuning of delta-protocadherin adhesion through combinatorial diversity
eLife 7:e41050.
https://doi.org/10.7554/eLife.41050

Share this article

https://doi.org/10.7554/eLife.41050

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