Live imaging of the lymphatic vascular network using transgenic zebrafish

Authors

• HM Jung
• D Castranova
• MR Swift
• VN Pham
• M Venero Galanternik
• S Isogai
• MG Butler
• TS Mulligan
• BM Weinstein

Abstract

The lymphatic vascular system is essential for tissue fluid homeostasis, immune trafficking, and absorption of dietary fats. It is also critically involved in a wide range of diseases including lymphedema, cancer metastasis, inflammatory and immunological disorders, and metabolic disease. Despite its importance, we still know very little about this system. The difficulty in visualizing and experimentally manipulating lymphatic vessels in vivo has been one of the key roadblocks to increasing our understanding of this crucial system. We developed an mrc1a:egfp reporter transgenic zebrafish enabling high-resolution visualization and functional manipulation of lymphatic vessels in the optically clear, experimentally accessible zebrafish model. Our findings reveal a highly stereotyped lymphatic system that forms in a stepwise, carefully choreographed manner. These developing zebrafish lymphatics strongly resemble the developing lymphatics of humans, affirming the usefulness of the fish as an experimental model for lymphangiogenesis. We show that these lymphatic vessels drain fluid from interstitial tissues. In addition, we show for the first time that immune cells traffic through zebrafish lymphatics, one of the key functional features of mammalian lymphatics. With the help of our newly developed transgenic tools, we are carrying out genetic screens for lymphatic-specific mutants and functional characterization of lymphatic-specific genes. We expect these to yield important insights into lymphangiogenesis and identify new targets for therapies directed against lymphatic-associated disease.

Scientific Focus Area: Developmental Biology

This page was last updated on Friday, March 26, 2021