PUBLICATION
Selective regulation of arterial branching morphogenesis by synectin
- Authors
- Chittenden, T.W., Claes, F., Lanahan, A.A., Autiero, M., Palac, R.T., Tkachenko, E.V., Elfenbein, A., Ruiz de Almodovar, C., Dedkov, E., Tomanek, R., Li, W., Westmore, M., Singh, J., Horowitz, A., Mulligan-Kehoe, M.J., Moodie, K.L., Zhuang, Z.W., Carmeliet, P., and Simons, M.
- ID
- ZDB-PUB-060616-18
- Date
- 2006
- Source
- Developmental Cell 10(6): 783-795 (Journal)
- Registered Authors
- Simons, Michael
- Keywords
- SIGNALING, DEVBIO
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing
- Animals
- Arteries/abnormalities
- Arteries/cytology
- Arteries/embryology*
- Arteries/growth & development*
- Carrier Proteins/chemistry
- Carrier Proteins/genetics
- Carrier Proteins/metabolism
- Cell Movement
- Cell Proliferation
- Cells, Cultured
- Embryo, Nonmammalian
- Endothelial Cells/cytology
- Endothelial Cells/physiology
- Endothelium, Vascular/cytology
- Female
- Femoral Artery/cytology
- Gene Expression Regulation
- Gene Expression Regulation, Developmental
- Mice
- Mice, Knockout
- Morphogenesis*
- Myocardium/cytology
- Neuropeptides/deficiency*
- Neuropeptides/genetics
- Pregnancy
- Venae Cavae/cytology
- Zebrafish/embryology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 16740480 Full text @ Dev. Cell
Citation
Chittenden, T.W., Claes, F., Lanahan, A.A., Autiero, M., Palac, R.T., Tkachenko, E.V., Elfenbein, A., Ruiz de Almodovar, C., Dedkov, E., Tomanek, R., Li, W., Westmore, M., Singh, J., Horowitz, A., Mulligan-Kehoe, M.J., Moodie, K.L., Zhuang, Z.W., Carmeliet, P., and Simons, M. (2006) Selective regulation of arterial branching morphogenesis by synectin. Developmental Cell. 10(6):783-795.
Abstract
Branching morphogenesis is a key process in the formation of vascular networks. To date, little is known regarding the molecular events regulating this process. We investigated the involvement of synectin in this process. In zebrafish embryos, synectin knockdown resulted in a hypoplastic dorsal aorta and hypobranched, stunted, and thin intersomitic vessels due to impaired migration and proliferation of angioblasts and arterial endothelial cells while not affecting venous development. Synectin(-/-) mice demonstrated decreased body and organ size, reduced numbers of arteries, and an altered pattern of arterial branching in multiple vascular beds while the venous system remained normal. Murine synectin(-/-) primary arterial, but not venous, endothelial cells showed decreased in vitro tube formation, migration, and proliferation and impaired polarization due to abnormal localization of activated Rac1. We conclude that synectin is involved in selective regulation of arterial, but not venous, growth and branching morphogenesis and that Rac1 plays an important role in this process.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping