Regulation of lymphatic-blood vessel separation by endothelial Rac1
- Gabriela D'Amico1,*†,
- Dylan T. Jones1,
- Emma Nye2,
- Karen Sapienza3,
- Antoine R. Ramjuan1,
- Louise E. Reynolds1,
- Stephen D. Robinson1,
- Vassiliki Kostourou1,8,
- Dolores Martinez4,
- Deborah Aubyn5,
- Richard Grose6,
- Gareth J. Thomas3,
- Bradley Spencer-Dene2,9,
- Daniel Zicha5,
- Derek Davies4,
- Victor Tybulewicz7 and
- Kairbaan M. Hodivala-Dilke1,†
- 1Adhesion 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
- 2Experimental Histopathology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK
- 3Centre for Tumour Biology, 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
- 4Fluorescence Activated Cell Sorting Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK
- 5Light Microscopy Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK
- 6Growth Factor Signalling 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
- 7Division of Immune Cell Biology, National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK
- 8BSRC Alexander Fleming, 34 Fleming street, 166 72 Vari, Athens, Greece
- 9Histopathology, Imperial College London, London, W12 0NN, UK
- † Authors for correspondence (Gabriela.Damico{at}Helsinki.FI; K.Hodivala-Dilke{at}qmul.ac.uk)
Summary
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+;Rac1fl/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.
Footnotes
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↵* Present address: Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, P.O.B. 63, 00014, Helsinki, Finland
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Supplementary material
Supplementary material for this article is available at http://dev.biologists.org/cgi/content/full/136/23/4043/DC1
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- Accepted September 29, 2009.
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