Pruning of blood vessels: Cells can fuse with themselves

Self-fusion observed in vertebrates for the first time

The formation of blood vessels follows a complicated architectural plan. "At a first glance, the plan for vascular regression seems to be the same but it must differ at the molecular level," explains Markus Affolter. During vascular regression, most of the cells consecutively migrate and incorporate into the neighboring functional vessels. The last single cell that remains in the pruning vessel reaches around the lumen and the membrane margins of this cell undergo fusion thus closing the vessel and assuring its tightness. This process, named cell self-fusion, ensures a controlled closure of a regressive blood vessel thus preventing blood leakage. For the first time this self-fusion of cells has been observed in vertebrates, the group humans also belong to. "Such cell behavior was so far only known in simpler organisms such as nematodes," explains Markus Affolter.

Greater plasticity through self-fusion

During the development of the vascular network, blood vessels are constantly formed but many of them are only required temporarily. Just like a disused arm of a highly branched river, the flow of fresh blood through these vessels is interrupted and the organism begins to prune this side arm. In this way the vascular system regulates itself, optimizing its blood circulation by pruning and recycling the unnecessary vessels with reduced blood flow and blood pressure. "This newly uncovered process is important for the understanding of blood vessel formation and regression on the cellular level, as this can also explain the extraordinary plasticity and changeability of the vascular system," says Anna Lenard, the first author of this publication. These investigations were performed on the zebrafish, as in this almost transparent fish the development of blood vessels can be observed in the living animal using modern microscopy techniques.

Relevance of self-fusion for cancer?

"How the cell recognizes its own membrane margins and how fusion with neighboring blood vessel cells is prevented, is not yet known," says Markus Affolter. Since a long time it has been postulated that each individual cell of an organism has its own code. "The regression process could partly confirm this theory," thinks Markus Affolter. Together with his team, he would like to investigate the self-fusion process more closely. As tumors require a well developed vascular system for their growth, a better understanding of the formation and regression of this network could open possibilities for the manipulation of such a system.