Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration
- Children's Hospital Los Angeles, United States
- University of California, Los Angeles, United States
- University of Münster, Germany
Abstract
The cardiac lymphatic vascular system and its potentially critical functions in heart patients have been largely underappreciated, in part due to a lack of experimentally accessible systems. We here demonstrate that cardiac lymphatic vessels develop in young adult zebrafish, using coronary arteries to guide their expansion down the ventricle. Mechanistically, we show that in cxcr4a mutants with defective coronary artery development, cardiac lymphatic vessels fail to expand onto the ventricle. In regenerating adult zebrafish hearts the lymphatic vasculature undergoes extensive lymphangiogenesis in response to a cryoinjury. A significant defect in reducing the scar size after cryoinjury is observed in zebrafish with impaired Vegfc/Vegfr3 signaling that fail to develop intact cardiac lymphatic vessels. These results suggest that the cardiac lymphatic system can influence the regenerative potential of the myocardium.
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 Figures 3, 4, 5 and 6
Article and author information
Author details
Michael RM Harrison
Stefan Schulte-Merker
Funding
National Heart, Lung, and Blood Institute (1R01HL130172)
- Ching-Ling Lien
Children's Hospital Los Angeles (2nd R01 and Team Awards)
- Ching-Ling Lien
American Heart Association (I81PA34180044)
- Ching-Ling Lien
California Institute for Regenerative Medicine (EDUC2-08418)
- Jessi Villafuerte
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Paul R Riley, University of Oxford, United Kingdom
Ethics
Animal experimentation: Animal experimentation: All zebrafish husbandry was performed under standard conditions, and all animal experiments were performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and following the ARRIVE guidelines provided by the National Centre for the Replacement, Refinement and Reduction of Animals in Research. All procedures were carried out as approved by the Children's Hospital Los Angeles (CHLA)institutional animal care and use committee (IACUC) protocols (#201-18 and 212-16).
Version history
- Received: October 12, 2018
- Accepted: September 24, 2019
- Accepted Manuscript published: November 8, 2019 (version 1)
- Version of Record published: November 27, 2019 (version 2)
Copyright
© 2019, Harrison 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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Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration
eLife 8:e42762.
https://doi.org/10.7554/eLife.42762
Further reading
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- Developmental Biology
- Stem Cells and Regenerative Medicine
Experiments on zebrafish show that the regeneration of the heart after an injury is supported by lymphatic vessels.
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- Developmental Biology
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