title: Selective regulation of arterial branching morphogenesis by synectin.
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.
authors.affiliation: Angiogenesis Research Center, Section of Cardiology, Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Chittenden
authors.forename: Filip
authors.initials: F
authors.lastname: Claes
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Lanahan
authors.forename: Monica
authors.initials: M
authors.lastname: Autiero
authors.forename: Robert T
authors.initials: RT
authors.lastname: Palac
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Tkachenko
authors.forename: Arye
authors.initials: A
authors.lastname: Elfenbein
authors.forename: Carmen
authors.initials: C
authors.lastname: Ruiz de Almodovar
authors.forename: Eduard
authors.initials: E
authors.lastname: Dedkov
authors.forename: Robert
authors.initials: R
authors.lastname: Tomanek
authors.forename: Weiming
authors.initials: W
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Westmore
authors.forename: Jai Pal
authors.initials: JP
authors.lastname: Singh
authors.forename: Arie
authors.initials: A
authors.lastname: Horowitz
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Mulligan-Kehoe
authors.forename: Karen L
authors.initials: KL
authors.lastname: Moodie
authors.forename: Zhen W
authors.initials: ZW
authors.lastname: Zhuang
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
mesh_terms: 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*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C511793:GIPC1 protein, zebrafish; C115271:Gipc1 protein, mouse; D009479:Neuropeptides; D029961:Zebrafish Proteins