Selective regulation of arterial branching morphogenesis by synectin.
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.
Chittenden
Thomas W
TW
Angiogenesis Research Center, Section of Cardiology, Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Claes
Filip
F
Lanahan
Anthony A
AA
Autiero
Monica
M
Palac
Robert T
RT
Tkachenko
Eugene V
EV
Elfenbein
Arye
A
Ruiz de Almodovar
Carmen
C
Dedkov
Eduard
E
Tomanek
Robert
R
Li
Weiming
W
Westmore
Michael
M
Singh
Jai Pal
JP
Horowitz
Arie
A
Mulligan-Kehoe
Mary Jo
MJ
Moodie
Karen L
KL
Zhuang
Zhen W
ZW
Carmeliet
Peter
P
Simons
Michael
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001158:Arteries / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005263:Femoral Artery / Q000166:cytology; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics; D011247:Pregnancy; D014684:Venae Cavae / Q000166:cytology; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C511793:GIPC1 protein, zebrafish; C115271:Gipc1 protein, mouse; D009479:Neuropeptides; D029961:Zebrafish Proteins