PUBLICATION
Role of synectin in lymphatic development in zebrafish and frogs
- Authors
- 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.
- ID
- ZDB-PUB-100719-62
- Date
- 2010
- Source
- Blood 116(17): 3356-3366 (Journal)
- Registered Authors
- Gjini, Evisa, Schulte-Merker, Stefan
- Keywords
- none
- MeSH Terms
-
- Lymphangiogenesis*
- Larva/genetics
- Larva/physiology
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/physiology*
- Neovascularization, Physiologic
- Xenopus Proteins/genetics
- Xenopus Proteins/metabolism*
- Animals
- Gene Silencing
- Thoracic Duct/embryology
- Thoracic Duct/growth & development
- Vascular Endothelial Growth Factor Receptor-3/genetics
- Humans
- Vascular Endothelial Growth Factor C/genetics
- Lymphatic Vessels/physiology*
- Neuropilin-2/genetics
- Carrier Proteins/genetics
- Carrier Proteins/metabolism*
- Zebrafish Proteins/genetics
- Xenopus laevis/genetics
- Xenopus laevis/physiology*
- Gene Expression Regulation, Developmental
- Cell Line
- PubMed
- 20631376 Full text @ Blood
Citation
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. (2010) Role of synectin in lymphatic development in zebrafish and frogs. Blood. 116(17):3356-3366.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping