title: Role of synectin in lymphatic development in zebrafish and frogs.
abstract: 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.
authors.affiliation: Vesalius Research Center, Vlaams Iustituut voor Biotechnologie, Katholieke Universiteit Leuven, Campus Gasthuisberg, Herestraat 49, Leuven, Belgium.
authors.forename: Karlien
authors.initials: K
authors.lastname: Hermans
authors.forename: Filip
authors.initials: F
authors.lastname: Claes
authors.forename: Wouter
authors.initials: W
authors.lastname: Vandevelde
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Ilse
authors.initials: I
authors.lastname: Geudens
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Orsenigo
authors.forename: Frederik
authors.initials: F
authors.lastname: De Smet
authors.forename: Evisa
authors.initials: E
authors.lastname: Gjini
authors.forename: Kristof
authors.initials: K
authors.lastname: Anthonis
authors.forename: Bin
authors.initials: B
authors.lastname: Ren
authors.forename: Dontcho
authors.initials: D
authors.lastname: Kerjaschki
authors.forename: Monica
authors.initials: M
authors.lastname: Autiero
authors.forename: Annelii
authors.initials: A
authors.lastname: Ny
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulte-Merker
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: 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
chemical_list: 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