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
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
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping