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Regulation of lymphatic-blood vessel separation by endothelial Rac1.

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dc.contributor.authorD'Amico, Gabriela
dc.contributor.authorJones, Dylan T
dc.contributor.authorNye, Emma
dc.contributor.authorSapienza, Karen
dc.contributor.authorRamjuan, Antoine R
dc.contributor.authorReynolds, Louise E
dc.contributor.authorRobinson, Stephen D
dc.contributor.authorKostourou, Vassiliki
dc.contributor.authorMartinez Garcia, Maria Dolores
dc.contributor.authorAubyn, Deborah
dc.contributor.authorGrose, Richard
dc.contributor.authorThomas, Gareth J
dc.contributor.authorSpencer-Dene, Bradley
dc.contributor.authorZicha, Daniel
dc.contributor.authorDavies, Derek
dc.contributor.authorTybulewicz, Victor
dc.contributor.authorHodivala-Dilke, Kairbaan M
dc.contributor.funderWellcome Trust
dc.date.accessioned2024-02-01T12:12:18Z
dc.date.available2024-02-01T12:12:18Z
dc.date.issued2009-12
dc.description.abstractSprouting 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.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipWe thank Dr Christiana Ruhrberg for assistance with the hindbrain model; Mitchel Germain for assistance with experiments; Garry Saunders, Colin Wren, Colin Pegrum, Claire Darnborough, Clare Watkins and Emma Murray for technical assistance with animals; Drs John Collard and Vania Braga for providing the GST-PAK-CRIB construct; Prof. Dietmar Vestweber for providing the endomucin antibody; Prof. Reinhard Fässler for providing Tie1-Cre mice; Prof. Kari Alitalo and Dr Tuomas Tammela for providing Vegfr3+/- mice; Takako Makita for technical advice on the India ink injections; and Prof. Peter Mortimer, Prof. Ian Hart and Prof. Tanya Petrova for their critical comments on the manuscript. G.D., E.N., A.R.R., S.D.R., L.E.R., V.K., K.S., D.M., D.A., B.S.-D., D.Z., D.D. and K.M.H.-D. were funded by Cancer Research UK. R.G. was funded by The Wellcome Trust. V.T. was funded by The Medical Research Council. D.T.J. was funded by Breast Cancer Campaign. G.T. was funded and by The Health Foundation, Royal College of Pathologists. Deposited in PMC for release after 6 months.es_ES
dc.format.number23es_ES
dc.format.page4043es_ES
dc.format.volume136es_ES
dc.identifier.citationDevelopment . 2009;136(23):4043-53.es_ES
dc.identifier.doi10.1242/dev.035014es_ES
dc.identifier.e-issn1477-9129es_ES
dc.identifier.journalDevelopment (Cambridge, England)es_ES
dc.identifier.pubmedID19906871es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/17410
dc.language.isoenges_ES
dc.publisherThe Company of Biologists
dc.relation.publisherversionhttps://doi.org/10.1242/dev.035014.es_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Citometría de Flujoes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshGene Expression Regulation, Developmentales_ES
dc.subject.meshAnimalses_ES
dc.subject.meshBlood Vesselses_ES
dc.subject.meshCell Separationes_ES
dc.subject.meshCells, Culturedes_ES
dc.subject.meshEmbryo, Mammalianes_ES
dc.subject.meshEndothelial Cellses_ES
dc.subject.meshEndothelium, Vasculares_ES
dc.subject.meshFluorescent Antibody Technique, Directes_ES
dc.subject.meshFluorescent Dyeses_ES
dc.subject.meshGalactosideses_ES
dc.subject.meshGene Deletiones_ES
dc.subject.meshImmunohistochemistryes_ES
dc.subject.meshIndoleses_ES
dc.subject.meshLymphatic Vesselses_ES
dc.subject.meshMicees_ES
dc.subject.meshMice, Transgenices_ES
dc.subject.meshNeovascularization, Physiologices_ES
dc.subject.meshRNA, Small Interferinges_ES
dc.subject.meshReceptor, TIE-2es_ES
dc.subject.meshTransfectiones_ES
dc.subject.meshbeta-Galactosidasees_ES
dc.subject.meshrac1 GTP-Binding Proteines_ES
dc.titleRegulation of lymphatic-blood vessel separation by endothelial Rac1.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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