Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins.
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.
Karkkainen
Marika J
MJ
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.
Haiko
Paula
P
Sainio
Kirsi
K
Partanen
Juha
J
Taipale
Jussi
J
Petrova
Tatiana V
TV
Jeltsch
Michael
M
Jackson
David G
DG
Talikka
Marja
M
Rauvala
Heikki
H
Betsholtz
Christer
C
Alitalo
Kari
K
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
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