Evolutionary Differences in the Vegf/Vegfr Code Reveal Organotypic Roles for the Endothelial Cell Receptor Kdr in Developmental Lymphangiogenesis
Adam J Vogrin, Neil Bower, Menachem J Gunzburg, Sally Roufail, Kazuhide S Okuda, Scott Paterson, Stephen J Headey, Steven A Stacker, Benjamin M Hogan, Marc G Achen
CELL REPORTS | CELL PRESS | Published : 2019
Lymphatic vascular development establishes embryonic and adult tissue fluid balance and is integral in disease. In diverse vertebrate organs, lymphatic vessels display organotypic function and develop in an organ-specific manner. In all settings, developmental lymphangiogenesis is considered driven by vascular endothelial growth factor (VEGF) receptor-3 (VEGFR3), whereas a role for VEGFR2 remains to be fully explored. Here, we define the zebrafish Vegf/Vegfr code in receptor binding studies. We find that while Vegfd directs craniofacial lymphangiogenesis, it binds Kdr (a VEGFR2 homolog) but surprisingly, unlike in mammals, does not bind Flt4 (VEGFR3). Epistatic analyses and characterization ..View full abstract
Imaging was performed at the Australian Cancer Research Foundation's Cancer Ultrastructure and Function Facility, Institute for Molecular Bioscience, University of Queensland. This work was supported by grants and a research fellowship from the National Health and Medical Research Council of Australia (NHMRC), and by the University of Queensland's Centre for Cardiac and Vascular Biology and the Operational Infrastructure Program of the Victorian government. B.M.H. was supported by a National Heart Foundation/NHMRC Career Development Fellowship.