A fisheye view on lymphangiogenesis

Zebrafish have been widely used to study vasculogenesis and angiogenesis, and the vascular system is one of the most intensively studied organ systems in teleosts. It is a little surprising, therefore, that the development of the zebrafish lymphatic network has only been investigated in any detail for less than a decade now. In those last few years, however, significant progress has been made. Due to favorable imaging possibilities within the early zebrafish embryo, we have a very good understanding of what cellular behavior accompanies the formation of the lymphatic system and which cells within the vasculature are destined to contribute to lymphatic vessels. The migration routes of future lymphatic endothelial cells have been monitored in great detail, and a number of transgenic lines have been developed that help to distinguish between arterial, venous, and lymphatic fates in vivo. Furthermore, both forward and reverse genetic tools have been systematically employed to unravel which genes are involved in the process. Not surprisingly, a number of known players were identified (such as vegfc and flt4), but work on zebrafish has also distinguished genes and proteins that had not previously been connected to lymphangiogenesis. Here, we will review these topics and also compare the equivalent stages of lymphatic development in zebrafish and mice. We will, in addition, highlight some of those studies in zebrafish that have helped to identify and to further characterize human disease conditions