Innervation modulates the functional connectivity between pancreatic endocrine cells

  1. Yu Hsuan Carol Yang  Is a corresponding author
  2. Linford JB Briant
  3. Christopher A Raab
  4. Sri Teja Mullapudi
  5. Hans-Martin Maischein
  6. Koichi Kawakami
  7. Didier YR Stainier  Is a corresponding author
  1. Max Planck Institute for Heart and Lung Research, Germany
  2. University of Oxford, United Kingdom
  3. National Institute of Genetics, Japan

Abstract

The importance of pancreatic endocrine cell activity modulation by autonomic innervation has been debated. To investigate this question, we established an in vivo imaging model that also allows chronic and acute neuromodulation with genetic and optogenetic tools. Using the GCaMP6s biosensor together with endocrine cell fluorescent reporters, we imaged calcium dynamics simultaneously in multiple pancreatic islet cell types in live animals in control states and upon changes in innervation. We find that by 4 days post fertilization in zebrafish, a stage when islet architecture is reminiscent of that in adult rodents, prominent activity coupling between beta cells is present in basal glucose conditions. Furthermore, we show that both chronic and acute loss of nerve activity result in diminished beta-beta and alpha-beta activity coupling. Pancreatic nerves are in contact with all islet cell types, but predominantly with beta and delta cells. Surprisingly, a subset of delta cells with detectable peri-islet neural activity coupling had significantly higher homotypic coupling with other delta cells suggesting that some delta cells receive innervation that coordinates their output. Overall, these data show that innervation plays a vital role in the maintenance of homotypic and heterotypic cellular connectivity in pancreatic islets, a process critical for islet function.

Data availability

All data generated or analysed during this study are included in the manuscript, figures, and figure legends. Source data files have been provided for Figures 1, 2, 3, and 5.

Article and author information

Author details

  1. Yu Hsuan Carol Yang

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    For correspondence
    Carol.Yang@mpi-bn.mpg.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6663-0302
  2. Linford JB Briant

    Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3619-3177
  3. Christopher A Raab

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  4. Sri Teja Mullapudi

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3916-8148
  5. Hans-Martin Maischein

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  6. Koichi Kawakami

    Division of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Japan
    Competing interests
    Koichi Kawakami, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9993-1435
  7. Didier YR Stainier

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    For correspondence
    Didier.Stainier@mpi-bn.mpg.de
    Competing interests
    Didier YR Stainier, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0382-0026

Funding

Max Planck Society

  • Didier YR Stainier

Canadian Institutes of Health Research

  • Yu Hsuan Carol Yang

Human Frontier Science Program (LT000159/2015)

  • Yu Hsuan Carol Yang

EMBO (ALTF 773-2014)

  • Yu Hsuan Carol Yang

NIG-JOINT

  • Yu Hsuan Carol Yang

AMED

  • Koichi Kawakami

Wellcome Trust

  • Linford JB Briant

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

Reviewing Editor

  1. Lori Sussel, University of Colorado Anschutz Medical Campus, United States

Ethics

Animal experimentation: All zebrafish husbandry was performed under standard conditions in accordance with institutional (MPG) and national ethical and animal welfare guidelines (Proposal numbers: B2/1041, B2/Anz. 1007, B2/1218). All procedures conform to the guidelines from Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes.

Version history

  1. Received: November 1, 2020
  2. Preprint posted: November 5, 2020 (view preprint)
  3. Accepted: April 3, 2022
  4. Accepted Manuscript published: April 4, 2022 (version 1)
  5. Version of Record published: April 13, 2022 (version 2)

Copyright

© 2022, Yang 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. Yu Hsuan Carol Yang
  2. Linford JB Briant
  3. Christopher A Raab
  4. Sri Teja Mullapudi
  5. Hans-Martin Maischein
  6. Koichi Kawakami
  7. Didier YR Stainier
(2022)
Innervation modulates the functional connectivity between pancreatic endocrine cells
eLife 11:e64526.
https://doi.org/10.7554/eLife.64526

Share this article

https://doi.org/10.7554/eLife.64526

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