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

Research paper by Karina.Yaniv@weizmann.ac.il (Brian C Raftrey, Karina.Yaniv@weizmann.ac.il (Dana Gancz, Karina.Yaniv@weizmann.ac.il (Didier Y Stainier, Karina.Yaniv@weizmann.ac.il (Gal Perlmoter, Karina.Yaniv@weizmann.ac.il (Hila Raviv, Karina.Yaniv@weizmann.ac.il (Jonathan Semo, Karina.Yaniv@weizmann.ac.il (Karina Yaniv, Karina.Yaniv@weizmann.ac.il (Kenneth D Poss, Karina.Yaniv@weizmann.ac.il (Kristy Red-Horse, Karina.Yaniv@weizmann.ac.il (Noga Moshe, Karina.Yaniv@weizmann.ac.il (Ofra Golani, Karina.Yaniv@weizmann.ac.il (Ravi Karra, Karina.Yaniv@weizmann.ac.il (Rubén Marín-Juez, Karina.Yaniv@weizmann.ac.il (Ryota L Matsuoka, Karina.Yaniv@weizmann.ac.il (Yoseph Addadi

Indexed on: 10 Nov '19Published on: 08 Nov '19Published in: eLife



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.