The growth of hierarchical blood vessel networks occurs by angiogenesis. During this process, new vessel growth is accompanied by the removal of redundant vessel segments by selective vessel regression (‘pruning’) and a reduction in endothelial cell (EC) density in order to establish an efficient, hierarchical network. EC apoptosis has long been recognised for its association with angiogenesis, but its contribution to this process has remained unclear. We generated mice in which EC apoptosis was blocked by tissue-specific deletion of the apoptosis effector proteins BAK and BAX. Using the retina as a model, we found that apoptosis made a minor contribution to the efficiency of capillary regression around arteries where apoptosis was most concentrated, but was otherwise dispensable for vessel pruning. Instead, apoptosis was necessary for the removal of non-perfused vessel segments and the reduction in EC density that occurs during vessel maturation. In the absence of apoptosis, increased EC density resulted in an increase in the diameter of capillaries, but not arteries or veins. Our findings show that apoptosis does not influence the number of vessels generated during angiogenesis. Rather it removes non-perfused vessel segments and regulates EC number during vessel maturation, which has vessel-specific consequences for vessel diameter.
The authors declare no competing or financial interests.
E.C.W. performed research, analysed data and wrote the paper. M.N.K., Z.L.G. and E.T. performed research. L.W. generated analytical tools and analysed data. G.D. analysed data. L.C. designed research, analysed data and wrote the paper.
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 to L.C.]; the Australian Research Council [Future Fellowships: 110100891 to L.C., 100100791 to G.D.]; and the L.E.W Carty Charitable Fund.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.137513.supplemental
- Received March 10, 2016.
- Accepted July 14, 2016.