Regulation of lymphatic-blood vessel separation by endothelial Rac1

D\'Amico G, Jones DT, Nye E, Sapienza K, Ramjuan AR, Reynolds LE, Robinson SD, Kostourou V, Martinez D, Aubyn D, Grose R, Thomas GJ, Spencer-Dene B, Zicha D, Davies D, Tybulewicz V, Hodivala-Dilke KM
Source: Development
Publication Date: (2009)
Issue: 136(23): 4043-53
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Endothelial, MV dermal blood, human neo
Species: human
Tissue Origin: dermal
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.