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ZFIN ID: ZDB-PUB-100719-62
Role of synectin in lymphatic development in zebrafish and frogs
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., and Carmeliet, P.
Date: 2010
Source: Blood   116(17): 3356-3366 (Journal)
Registered Authors: Gjini, Evisa, Schulte-Merker, Stefan
Keywords: none
MeSH Terms:
  • Animals
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism*
  • Cell Line
  • Gene Expression Regulation, Developmental
  • Gene Silencing
  • Humans
  • Larva/genetics
  • Larva/physiology
  • Lymphangiogenesis*
  • Lymphatic Vessels/physiology*
  • Neovascularization, Physiologic
  • Neuropilin-2/genetics
  • Thoracic Duct/embryology
  • Thoracic Duct/growth & development
  • Vascular Endothelial Growth Factor C/genetics
  • Vascular Endothelial Growth Factor Receptor-3/genetics
  • Xenopus Proteins/genetics
  • Xenopus Proteins/metabolism*
  • Xenopus laevis/genetics
  • Xenopus laevis/physiology*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
PubMed: 20631376 Full text @ Blood
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 TD arises from parachordal lymphangioblast (PL) cells, which in turn derive from secondary lymphangiogenic sprouts from the posterior cardinal vein (PCV). Morpholino knockdown of synectin in zebrafish impaired formation of the thoracic duct (TD), 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 ECs (LECs). Molecular analysis further revealed that synectin regulated Sox18-induced expression of Prox-1 and VEGFC-induced migration of LECs in vitro. These findings reveal a novel role for synectin in lymphatic development.