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Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3.

TitleNeuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3.
Publication TypeJournal Article
Year of Publication2010
AuthorsXu Y, Yuan L, Mak J, Pardanaud L, Caunt M, Kasman I, Larrivée B, Del Toro R, Suchting S, Medvinsky AL, Silva J, Yang J, Thomas J-L, Koch AW, Alitalo K, Eichmann A, Bagri A
JournalJ Cell Biol
Volume188
Issue1
Pagination115-30
Date Published2010 Jan 11
ISSN1540-8140
KeywordsAnimals, Cell Shape, Cells, Cultured, Endothelial Cells, Female, Lymphangiogenesis, Lymphatic Vessels, Male, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Transgenic, Neuropilin-2, Protein Binding, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor Receptor-3
Abstract

Vascular sprouting is a key process-driving development of the vascular system. In this study, we show that neuropilin-2 (Nrp2), a transmembrane receptor for the lymphangiogenic vascular endothelial growth factor C (VEGF-C), plays an important role in lymphatic vessel sprouting. Blocking VEGF-C binding to Nrp2 using antibodies specifically inhibits sprouting of developing lymphatic endothelial tip cells in vivo. In vitro analyses show that Nrp2 modulates lymphatic endothelial tip cell extension and prevents tip cell stalling and retraction during vascular sprout formation. Genetic deletion of Nrp2 reproduces the sprouting defects seen after antibody treatment. To investigate whether this defect depends on Nrp2 interaction with VEGF receptor 2 (VEGFR2) and/or 3, we intercrossed heterozygous mice lacking one allele of these receptors. Double-heterozygous nrp2vegfr2 mice develop normally without detectable lymphatic sprouting defects. In contrast, double-heterozygote nrp2vegfr3 mice show a reduction of lymphatic vessel sprouting and decreased lymph vessel branching in adult organs. Thus, interaction between Nrp2 and VEGFR3 mediates proper lymphatic vessel sprouting in response to VEGF-C.

DOI10.1083/jcb.200903137
Alternate JournalJ. Cell Biol.
PubMed ID20065093
PubMed Central IDPMC2812843