Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1
EC Watson, L Whitehead, RH Adams, G Dewson, L Coultas
CELL DEATH AND DIFFERENTIATION | NATURE PUBLISHING GROUP | Published : 2016
Angiogenesis is essential to match the size of blood vessel networks to the metabolic demands of growing tissues. While many genes and pathways necessary for regulating angiogenesis have been identified, those responsible for endothelial cell (EC) survival during angiogenesis remain largely unknown. We have investigated the in vivo role of myeloid cell leukemia 1 (MCL1), a pro-survival member of the BCL2 family, in EC survival during angiogenesis. EC-specific deletion of Mcl1 resulted in a dose-dependent increase in EC apoptosis in the angiogenic vasculature and a corresponding decline in vessel density. Our results suggest this apoptosis was independent of the BH3-only protein BIM. Despite ..View full abstract
Awarded by National Health and Medical Research Council, Australia
Awarded by Australian Research Council Future Fellowships
We thank M Scott and K Rogers for expert imaging assistance, E Trounson and MN Koenig for expert technical assistance, E Lanera, G Dabrowski and D Cooper for expert animal care and procedures, Douglas Green (St Jude Children's Research Hospital, Memphis) for Bax conditional allele mice, Masashi Yanagisawa (UT Southwestern) for Tie2-cre mice, A Strasser and P Bouillet (the Walter and Eliza Hall Institute) for generously providing Mcl1 conditional mice, Bim<SUP>-/-</SUP> mice and for informative discussion, RCA Symons (the Royal Melbourne Hospital), AK Voss (the Walter and Eliza Hall Institute) and members of the Development and Cancer Division (the Walter and Eliza Hall Institute) for informative discussion. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. This work was supported by the National Health and Medical Research Council, Australia (Project Grant: 1010638). LC and GD are supported by Australian Research Council Future Fellowships (LC: 110100891. GD: 100100791). LC is supported by the LEW Carty Charitable Fund.