Regulation of lymphatic-blood vessel separation by endothelial Rac1.
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.
D'Amico
Gabriela
G
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
Jones
Dylan T
DT
Nye
Emma
E
Sapienza
Karen
K
Ramjuan
Antoine R
AR
Reynolds
Louise E
LE
Robinson
Stephen D
SD
Kostourou
Vassiliki
V
Martinez
Dolores
D
Aubyn
Deborah
D
Grose
Richard
R
Thomas
Gareth J
GJ
Spencer-Dene
Bradley
B
Zicha
Daniel
D
Davies
Derek
D
Tybulewicz
Victor
V
Hodivala-Dilke
Kairbaan M
KM
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*
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