Zebrafish Models of Induced Lymphangiogenesis: Current Advancements and Therapeutic Discovery

Lymphangiogenesis, the formation of new lymphatic vessels, is essential for embryonic development and the maintenance of tissue fluid balance, as well as for responding to physiological challenges such as injury, inflammation, and oedema. This process is also aberrantly activated in pathological conditions including lymphatic anomalies and cancer. Understanding the molecular and cellular mechanisms regulating induced lymphangiogenesis in various conditions is critical for the development of novel anti- or pro-lymphangiogenic therapeutic strategies. In recent years, the zebrafish has emerged as an important model organism for studying both physiological and pathological lymphangiogenesis. Its optical transparency, conserved lymphatic architecture and signalling pathways, and amenability to genetic manipulation and drug screening make it an especially well-suited model. In this review, we highlight zebrafish models used to investigate induced lymphangiogenesis in the context of regeneration, inflammation, fluid imbalance, and congenital lymphatic anomalies. We will also demonstrate how zebrafish are used to discover new drugs targeting lymphatic vessels under various conditions. Finally, we will discuss the current limitations of using zebrafish to model induced lymphangiogenesis and highlight potential future directions. The findings presented in this review underscore the undeniable value the zebrafish model brings to lymphatic research and therapeutic discovery.