Lymphangiogenesis, the formation of lymphatic vessels is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in zebrafish. We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of a proper trunk lymphatic network and leading to edema development. We show that Sorbs1 is probably not part of the Vegfc signaling, but instead might interacts with the BMP pathways. Mechanistically, we show that Sorbs1 controls FAK/Src signaling to impact on Rac1 and RhoA GTPases-regulated cytoskeleton processes. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contact rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties. Our data thus establish Sorbs1 as an important regulator of lymphangiogenesis distinct from the Vegfc signaling axis, increasing our understanding of context-specific vascular and lymphatic development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.