A new mode of pancreatic islet innervation revealed by live imaging in zebrafish

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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

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.
Koichi Kawakami

Division of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Japan

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-9993-1435
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.

"This ORCID iD identifies the author of this article:" 0000-0002-0382-0026

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).

Copyright

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.