A genetic Xenopus laevis tadpole model to study lymphangiogenesis.
Lymph vessels control fluid homeostasis, immunity and metastasis. Unraveling the molecular basis of lymphangiogenesis has been hampered by the lack of a small animal model that can be genetically manipulated. Here, we show that Xenopus tadpoles develop lymph vessels from lymphangioblasts or, through transdifferentiation, from venous endothelial cells. Lymphangiography showed that these lymph vessels drain lymph, through the lymph heart, to the venous circulation. Morpholino-mediated knockdown of the lymphangiogenic factor Prox1 caused lymph vessel defects and lymphedema by impairing lymphatic commitment. Knockdown of vascular endothelial growth factor C (VEGF-C) also induced lymph vessel defects and lymphedema, but primarily by affecting migration of lymphatic endothelial cells. Knockdown of VEGF-C also resulted in aberrant blood vessel formation in tadpoles. This tadpole model offers opportunities for the discovery of new regulators of lymphangiogenesis.
Ny
Annelii
A
Flanders Interuniversity Institute for Biotechnology, Center for Transgene Technology and Gene Therapy, Campus Gasthuisberg O&N, Herestraat 49, KULeuven, Leuven, B-3000.
Koch
Marta
M
Schneider
Martin
M
Neven
Elke
E
Tong
Ricky T
RT
Maity
Sunit
S
Fischer
Christian
C
Plaisance
Stephane
S
Lambrechts
Diether
D
Héligon
Christophe
C
Terclavers
Sven
S
Ciesiolka
Malgorzata
M
Kälin
Roland
R
Man
Wing Yan
WY
Senn
Irena
I
Wyns
Sabine
S
Lupu
Florea
F
Brändli
André
A
Vleminckx
Kris
K
Collen
Désiré
D
Dewerchin
Mieke
M
Conway
Edward M
EM
Moons
Lieve
L
Jain
Rakesh K
RK
Carmeliet
Peter
P
D000818:Animals; D018398:Homeodomain Proteins / Q000502:physiology; D007814:Larva / Q000235:genetics / Q000254:growth & development; D042583:Lymphangiogenesis / Q000235:genetics / Q000502:physiology*; D008208:Lymphatic System / Q000033:anatomy & histology / Q000254:growth & development; D025521:Tumor Suppressor Proteins; D014982:Xenopus laevis / Q000235:genetics* / Q000254:growth & development*; D000098551:Prospero-Related Homeobox 1 Protein
D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein