Vasohibin-1 mediated tubulin detyrosination selectively regulates secondary sprouting and lymphangiogenesis in the zebrafish trunk

Previous studies have shown that Vasohibin-1 (Vash-1) is stimulated by VEGFs in endothelial cells and that its overexpression interferes with angiogenesisin vivo. Recently, Vasohibin-1 was found to mediate tubulin detyrosination, a post-translational modification that is implicated in many cell functions, such as cell division. Here we used the zebrafish embryo to investigate the cellular and subcellular mechanisms of Vash-1 on endothelial microtubules during formation of the trunk vasculature. We show that microtubules within venous-derived secondary sprouts are strongly and selectively detyrosinated in comparison with other endothelial cells, and that this difference is lost uponvash-1knockdown. Vasohibin-1 depletion in zebrafish specifically affected secondary sprouting from the posterior cardinal vein, increasing both the number of sprouts and endothelial cell divisions. We show that altering secondary sprout numbers and structure uponvash-1depletion leads to a failure in the development and specification of lymphatic vessels of the zebrafish trunk.