XB-ART-1468Nat Med September 1, 2005; 11 (9): 998-1004.
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.
PubMed ID: 16116431
Article link: Nat Med
Grant support: CA-85140 NCI NIH HHS
Genes referenced: prox1 vegfa vegfc
Morpholinos referenced: prox1 MO1 prox1 MO2 vegfc MO1