title: Regulation of lymphatic-blood vessel separation by endothelial Rac1.
abstract: Sprouting angiogenesis and lymphatic-blood vessel segregation both involve the migration of endothelial cells, but the precise migratory molecules that govern the decision of blood vascular endothelial cells to segregate into lymphatic vasculature are unknown. Here, we deleted endothelial Rac1 in mice (Tie1-Cre(+);Rac1(fl/fl)) and revealed, unexpectedly, that whereas blood vessel morphology appeared normal, lymphatic-blood vessel separation was impaired, with corresponding edema, haemorrhage and embryonic lethality. Importantly, normal levels of Rac1 were essential for directed endothelial cell migratory responses to lymphatic-inductive signals. Our studies identify Rac1 as a crucial part of the migratory machinery required for endothelial cells to separate and form lymphatic vasculature.
authors.affiliation: Adhesion and Angiogenesis Laboratory, Institute of Cancer and Cancer Research UK, Bart's & The London Queen Mary's School of Medicine & Dentistry, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK. Gabriela.Damico@Helsinki.FI
authors.forename: Gabriela
authors.initials: G
authors.lastname: D'Amico
authors.forename: Dylan T
authors.initials: DT
authors.lastname: Jones
authors.forename: Emma
authors.initials: E
authors.lastname: Nye
authors.forename: Karen
authors.initials: K
authors.lastname: Sapienza
authors.forename: Antoine R
authors.initials: AR
authors.lastname: Ramjuan
authors.forename: Louise E
authors.initials: LE
authors.lastname: Reynolds
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Robinson
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kostourou
authors.forename: Dolores
authors.initials: D
authors.lastname: Martinez
authors.forename: Deborah
authors.initials: D
authors.lastname: Aubyn
authors.forename: Richard
authors.initials: R
authors.lastname: Grose
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Thomas
authors.forename: Bradley
authors.initials: B
authors.lastname: Spencer-Dene
authors.forename: Daniel
authors.initials: D
authors.lastname: Zicha
authors.forename: Derek
authors.initials: D
authors.lastname: Davies
authors.forename: Victor
authors.initials: V
authors.lastname: Tybulewicz
authors.forename: Kairbaan M
authors.initials: KM
authors.lastname: Hodivala-Dilke
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct; D005456:Fluorescent Dyes / Q000378:metabolism; D005697:Galactosides / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D007211:Indoles / Q000378:metabolism; D042601:Lymphatic Vessels / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D005697:Galactosides; D007211:Indoles; D034741:RNA, Small Interfering; C007293:DAPI; D042787:Receptor, TIE-2; D001616:beta-Galactosidase; D020830:rac1 GTP-Binding Protein; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside