Role of synectin in lymphatic development in zebrafish and frogs. Blood 2010 Oct 28;116(17):3356-66
Date
07/16/2010Pubmed ID
20631376Pubmed Central ID
PMC3490102DOI
10.1182/blood-2009-11-254557Scopus ID
2-s2.0-78049372104 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
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.
Author List
Hermans K, Claes F, Vandevelde W, Zheng W, Geudens I, Orsenigo F, De Smet F, Gjini E, Anthonis K, Ren B, Kerjaschki D, Autiero M, Ny A, Simons M, Dewerchin M, Schulte-Merker S, Dejana E, Alitalo K, Carmeliet PMESH terms used to index this publication - Major topics in bold
AnimalsCarrier Proteins
Cell Line
Gene Expression Regulation, Developmental
Gene Silencing
Humans
Larva
Lymphangiogenesis
Lymphatic Vessels
Neovascularization, Physiologic
Neuropilin-2
Thoracic Duct
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor Receptor-3
Xenopus Proteins
Xenopus laevis
Zebrafish
Zebrafish Proteins
