TY - JOUR
T1 - Selective Regulation of Arterial Branching Morphogenesis by Synectin
AU - Chittenden, Thomas W.
AU - Claes, Filip
AU - Lanahan, Anthony A.
AU - Autiero, Monica
AU - Palac, Robert T.
AU - Tkachenko, Eugene V.
AU - Elfenbein, Arye
AU - Ruiz de Almodovar, Carmen
AU - Dedkov, Eduard
AU - Tomanek, Robert
AU - Li, Weiming
AU - Westmore, Michael
AU - Singh, Jai Pal
AU - Horowitz, Arie
AU - Mulligan-Kehoe, Mary Jo
AU - Moodie, Karen L.
AU - Zhuang, Zhen W.
AU - Carmeliet, Peter
AU - Simons, Michael
PY - 2006/6
Y1 - 2006/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.devcel.2006.03.012
DO - 10.1016/j.devcel.2006.03.012
M3 - Article
C2 - 16740480
AN - SCOPUS:33744483170
SN - 1534-5807
VL - 10
SP - 783
EP - 795
JO - Developmental Cell
JF - Developmental Cell
IS - 6
ER -