title: Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins.
abstract: Lymphatic vessels are essential for immune surveillance, tissue fluid homeostasis and fat absorption. Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development. In Vegfc-/- mice, endothelial cells commit to the lymphatic lineage but do not sprout to form lymph vessels. Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating VEGF receptor 3 specificity. The lack of lymphatic vessels resulted in prenatal death due to fluid accumulation in tissues, and Vegfc+/- mice developed cutaneous lymphatic hypoplasia and lymphedema. Our results indicate that VEGF-C is the paracrine factor essential for lymphangiogenesis, and show that both Vegfc alleles are required for normal lymphatic development.
authors.affiliation: Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, PO Box 63, 00014 Helsinki, Finland.
authors.forename: Marika J
authors.initials: MJ
authors.lastname: Karkkainen
authors.forename: Paula
authors.initials: P
authors.lastname: Haiko
authors.forename: Kirsi
authors.initials: K
authors.lastname: Sainio
authors.forename: Juha
authors.initials: J
authors.lastname: Partanen
authors.forename: Jussi
authors.initials: J
authors.lastname: Taipale
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Petrova
authors.forename: Michael
authors.initials: M
authors.lastname: Jeltsch
authors.forename: David G
authors.initials: DG
authors.lastname: Jackson
authors.forename: Marja
authors.initials: M
authors.lastname: Talikka
authors.forename: Heikki
authors.initials: H
authors.lastname: Rauvala
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
mesh_terms: D000818:Animals; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000235:genetics / Q000502:physiology*; D042601:Lymphatic Vessels / Q000196:embryology*; D008209:Lymphedema / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D042582:Vascular Endothelial Growth Factor C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000502:physiology
chemical_list: D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse; D040262:Receptors, Vascular Endothelial Growth Factor; D040321:Vascular Endothelial Growth Factor Receptor-3