Title: Role of VEGF-D and VEGFR-3 in developmental lymphangiogenesis, a chemicogenetic study in Xenopus tadpoles
Authors: Ny, Annelii
Koch, Marta
Vandevelde, Wouter
Schneider, Martin
Fischer, Christian
Diez-Juan, Antonio
Neven, Elke
Geudens, Ilse
Maity, Sunit
Moons, Lieve
Plaisance, Stéphane
Lambrechts, Diether
Carmeliet, Peter
Dewerchin, Mieke # ×
Issue Date: Sep-2008
Series Title: Blood vol:112 issue:5 pages:1740-1749
Abstract: The importance of the lymphangiogenic factor VEGF-D and its receptor VEGFR-3 in early lymphatic development remains largely unresolved. We therefore investigated their role in Xenopus laevis tadpoles, a small animal model allowing chemicogenetic dissection of developmental lymphangiogenesis. Single morpholino antisense oligo knockdown of xVEGF-D did not affect lymphatic commitment, but transiently impaired lymphatic endothelial cell (LEC) migration. Notably, combined knockdown of xVEGF-D with xVEGF-C at suboptimal morpholino concentrations resulted in more severe migration defects and lymphedema formation than the corresponding single knockdowns. Knockdown of VEGFR-3 or treatment with the VEGFR-3 inhibitor MAZ51 similarly impaired lymph vessel formation and function and caused pronounced edema. VEGFR-3 silencing by morpholino knockdown, MAZ51 treatment, or xVEGF-C/D double knockdown also resulted in dilation and dysfunction of the lymph heart. These findings document a critical role of VEGFR-3 in embryonic lymphatic development and function, and reveal a previously unrecognized modifier role of VEGF-D in the regulation of embryonic lymphangiogenesis in frog embryos.
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Molecular Genetics Section (-)
Animal Physiology and Neurobiology Section - miscellaneous
Molecular and Vascular Biology
Laboratory of Neurogenetics (-)
Laboratory of Translational Genetics (VIB-KU Leuven Center for Cancer Biology)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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