Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration
- Weizmann Institute of Science, Israel
- Stanford University, United States
- Max Planck Institute for Heart and Lung Research, Germany
- Duke University, United States
Abstract
In recent years there has been increasing interest in the role of lymphatics in organ repair and regeneration, due to their importance in immune surveillance and fluid homeostasis. Experimental approaches aimed at boosting lymphangiogenesis following myocardial infarction in mice, were shown to promote healing of the heart. Yet, the mechanisms governing cardiac lymphatic growth remain unclear. Here we identify two distinct lymphatic populations in the hearts of zebrafish and mouse, one that forms through sprouting lymphangiogenesis, and the other by coalescence of isolated lymphatic cells. By tracing the development of each subset, we reveal diverse cellular origins and differential response to signaling cues. Finally, we show that lymphatic vessels are required for cardiac regeneration in zebrafish as mutants lacking lymphatics display severely impaired regeneration capabilities. Overall, our results provide novel insight into the mechanisms underlying lymphatic formation during development and regeneration, opening new avenues for interventions targeting specific lymphatic populations.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files
Article and author information
Author details
Funding
H2020 European Research Council (335605)
- Karina Yaniv
National Institutes of Health (R01 HL131319)
- Kenneth D Poss
National Institutes of Health (R01 136182)
- Kenneth D Poss
American Heart Association
- Kenneth D Poss
Fondation Leducq
- Kenneth D Poss
United States-Israel Binational Science Foundation (2015289)
- Karina Yaniv
Minerva Foundation (712610)
- Karina Yaniv
H&M Kimmel Inst. for Stem cell research, the Estate of Emile Mimran
- Karina Yaniv
National Institutes of Health (RO1-HL128503)
- Kristy Red-Horse
New York Stem Cell Foundation
- Kristy Red-Horse
Max-Planck-Gesellschaft
- Didier Y Stainier
Fondation Leducq
- Didier Y Stainier
National Institutes of Health (R01 HL081674)
- Kenneth D Poss
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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 (#01470218-2) of the Weizmann Institute of Science. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Weizmann Institute of Science. All surgery in fish was performed under tricaine anesthesia, and every effort was made to minimize suffering.
Copyright
© 2019, Gancz 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.
Metrics
-
- 4,528
- views
-
- 745
- downloads
-
- 80
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration
eLife 8:e44153.
https://doi.org/10.7554/eLife.44153
Further reading
-
- 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.
-
- Cell Biology
- Developmental Biology
In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronized sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.
