Role of synectin in lymphatic development in zebrafish and frogs

TY - JOUR

T1 - Role of synectin in lymphatic development in zebrafish and frogs

AU - Hermans, K.

AU - Claes, F.

AU - Vandevelde, W.

AU - Zheng, W.

AU - Geudens, I.

AU - Orsenigo, F.

AU - De Smet, F.

AU - Gjini, E.

AU - Anthonis, K.

AU - Ren, B.

AU - Kerjaschki, D.

AU - Autiero, M.

AU - Ny, A.

AU - Simons, M.

AU - Dewerchin, M.

AU - Schulte-Merker, S.

AU - Dejana, E.

AU - Alitalo, K.

AU - Carmeliet, P.

N1 - Reporting year: 2010

PY - 2010

Y1 - 2010

N2 - The molecular basis of lymphangiogenesis remains incompletely characterized. Here, we document a novel role for the PDZ domain-containing scaffold protein synectin in lymphangiogenesis using genetic studies in zebrafish and tadpoles. In zebrafish, the thoracic duct arises from parachordal lymphangioblast cells, which in turn derive from secondary lymphangiogenic sprouts from the posterior cardinal vein. Morpholino knockdown of synectin in zebrafish impaired formation of the thoracic duct, due to selective defects in lymphangiogenic but not angiogenic sprouting. Synectin genetically interacted with Vegfr3 and neuropilin-2a in regulating lymphangiogenesis. Silencing of synectin in tadpoles caused lymphatic defects due to an underdevelopment and impaired migration of Prox-1(+) lymphatic endothelial cells. Molecular analysis further revealed that synectin regulated Sox18-induced expression of Prox-1 and vascular endothelial growth factor C-induced migration of lymphatic endothelial cells in vitro. These findings reveal a novel role for synectin in lymphatic development.

AB - The molecular basis of lymphangiogenesis remains incompletely characterized. Here, we document a novel role for the PDZ domain-containing scaffold protein synectin in lymphangiogenesis using genetic studies in zebrafish and tadpoles. In zebrafish, the thoracic duct arises from parachordal lymphangioblast cells, which in turn derive from secondary lymphangiogenic sprouts from the posterior cardinal vein. Morpholino knockdown of synectin in zebrafish impaired formation of the thoracic duct, due to selective defects in lymphangiogenic but not angiogenic sprouting. Synectin genetically interacted with Vegfr3 and neuropilin-2a in regulating lymphangiogenesis. Silencing of synectin in tadpoles caused lymphatic defects due to an underdevelopment and impaired migration of Prox-1(+) lymphatic endothelial cells. Molecular analysis further revealed that synectin regulated Sox18-induced expression of Prox-1 and vascular endothelial growth factor C-induced migration of lymphatic endothelial cells in vitro. These findings reveal a novel role for synectin in lymphatic development.

U2 - 10.1182/blood-2009-11-254557

DO - 10.1182/blood-2009-11-254557

M3 - Article

SN - 0006-4971

VL - 116

SP - 3356

EP - 3366

JO - Blood

JF - Blood

IS - 17

ER -