Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration

• Main Authors: Dana Gancz, Brian C Raftrey, Gal Perlmoter, Rubén Marín-Juez, Jonathan Semo, Ryota L Matsuoka, Ravi Karra, Hila Raviv, Noga Moshe, Yoseph Addadi, Ofra Golani, Kenneth D Poss, Kristy Red-Horse, Didier YR Stainier, Karina Yaniv
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2019-11-01
• Series: eLife
• Subjects: lymphatics; cardiac; regeneration
• Online Access: https://elifesciences.org/articles/44153

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.