Role of synectin in lymphatic development in zebrafish and frogs.
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.
Hermans
Karlien
K
Vesalius Research Center, Vlaams Iustituut voor Biotechnologie, Katholieke Universiteit Leuven, Campus Gasthuisberg, Herestraat 49, Leuven, Belgium.
Claes
Filip
F
Vandevelde
Wouter
W
Zheng
Wei
W
Geudens
Ilse
I
Orsenigo
Fabrizio
F
De Smet
Frederik
F
Gjini
Evisa
E
Anthonis
Kristof
K
Ren
Bin
B
Kerjaschki
Dontcho
D
Autiero
Monica
M
Ny
Annelii
A
Simons
Michael
M
Dewerchin
Mieke
M
Schulte-Merker
Stefan
S
Dejana
Elisabetta
E
Alitalo
Kari
K
Carmeliet
Peter
P
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006801:Humans; D007814:Larva / Q000235:genetics / Q000502:physiology; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000502:physiology*; D018919:Neovascularization, Physiologic; D039943:Neuropilin-2 / Q000235:genetics; D013897:Thoracic Duct / Q000196:embryology / Q000254:growth & development; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics
D002352:Carrier Proteins; C511793:GIPC1 protein, zebrafish; D039943:Neuropilin-2; D042582:Vascular Endothelial Growth Factor C; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C493178:vascular endothelial growth factor C, zebrafish; D040321:Vascular Endothelial Growth Factor Receptor-3