Abstract
Pancreatic islets are innervated by autonomic and sensory nerves that influence their function. Analyzing the innervation process should provide insight into the nerve-endocrine interactions and their roles in development and disease. Here, using in vivo time-lapse imaging and genetic analyses in zebrafish, we determined the events leading to islet innervation. Comparable neural density in the absence of vasculature indicates that it is dispensable for early pancreatic innervation. Neural crest cells are in close contact with endocrine cells early in development. We find these cells give rise to neurons that extend axons towards the islet as they surprisingly migrate away. Specific ablation of these neurons partly prevents other neurons from migrating away from the islet resulting in diminished innervation. Thus, our studies establish the zebrafish as a model to interrogate mechanisms of organ innervation, and reveal a novel mode of innervation whereby neurons establish connections with their targets before migrating away.
Data availability
All data generated/analysed during this study are included in the manuscript. Individual replicates along with the means+/- SEM are plotted for all numerical data in the figures.
Article and author information
Author details
Didier YR Stainier
Funding
Max Planck Society (Open-access funding)
- Didier YR Stainier
Human Frontier Science Program (Long-Term Fellowship)
- Yu Hsuan Carol Yang
European Molecular Biology Organization (Long-Term Fellowship)
- Yu Hsuan Carol Yang
Canadian Institutes of Health Research (CIHR Fellowship)
- Yu Hsuan Carol Yang
Japan Agency for Medical Research and Development (NBRP)
- Koichi Kawakami
National Institute of Genetics (NIG-JOINT Collaborative Research (A2))
- Yu Hsuan Carol Yang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All zebrafish husbandry was performed under standard conditions in accordance with institutional (MPG) and national ethical and animal welfare guidelines approved by the ethics committee for animal experiments at the Regierungspräsidium Darmstadt, Germany (permit numbers B2/1138 and B2/Anz. 1007).
Reviewing Editor
- Judith Eisen, University of Oregon, United States
Publication history
- Received: December 21, 2017
- Accepted: June 18, 2018
- Accepted Manuscript published: June 19, 2018 (version 1)
- Version of Record published: July 10, 2018 (version 2)
Copyright
© 2018, 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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