Blood vessels are vital for our body, transporting essential nutrients and oxygen through circulating blood. During vessel formation, cells first form local lumens, which then fuse to create a continuous tubular network. The junctions between the individual cells must be well sealed and stable to ensure vascular integrity and to prevent leakage.
In two studies, Prof. Markus Affolter’s team at the Biozentrum of the University of Basel has investigated blood vessel formation in zebrafish, revealing that the protein Rasip1 is crucial in the process of vascular lumen formation. Additionally, they discovered that contraction forces are vital in driving cell interactions, facilitating the continuous formation of vascular lumens. Rasip1 is essential for vessel formation.
In the study, the researchers showed that the Rasip1 protein is significantly involved in the early stages of lumen formation, which occurs at the adhesion site where two endothelial cells meet. Their investigation specifically centered on the junction between these two cells, known as the adhesion sites.
They found that this adhesion site evolves into a hollow structure resembling the two halves of a nutshell with a sticky adhesive ring on the side. In this transformation, the protein Rasip1 plays a key role.
“It moves the adhesion proteins from the center to the periphery and allows the lumen to inflate in between,” says Jianmin Yin.
In another study, the team examined the role of the research group investigating the function of contractile forces governed by the proteins Heg1 and Ccm1.
“We discovered that these contractile forces between the cells are essential. Only when their intensity is precisely regulated do cells interact correctly, enabling proper vessel formation,” explains first author Jianmin Yin.
The researchers have identified a mechanism whereby synchronized tensile forces at cell-cell junctions foster coordinated growth of blood vessels. “We found that tiny forces generated by the rhythmic contraction of cellular structures stabilize cell junctions and thereby help to maintain their shape,” says Heinz Georg Belting, who led the study.
By selectively activating these forces, the team was able to repair defective cell connections. This research advocates for the pivotal importance of these forces in maintaining a healthy vascular network.
Recent discoveries regarding the critical role of dynamic forces and protein regulation have significantly enhanced our understanding of blood vessel formation.
“It is still remarkable to observe this process in the living organism and derive new conclusions,” says Belting. “When the balance of forces at the cell junction is disrupted, or proteins misrelate the process, a stable organ structure cannot be formed, resulting in defective blood vessels develop.”
These research discoveries could pave the way for developing treatment strategies for vascular conditions such as aneurysms or peripheral arterial occlusive disease. In the future, the researchers intend to utilize biophysical techniques to investigate this process more thoroughly, aiming to gain a better understanding of the molecular mechanisms involved in blood vessel formation.
Journal reference:
- Jianmin Yin, Niels Schellinx, Ludovico Maggi, Kathrin Gundel, Cora Wiesner, Maria Paraskevi Kotini, Minkyoung Lee, Li-Kun Phng, Heinz-Georg Belting & Markus Affolter. Initiation of lumen formation from junctions via differential actomyosin contractility regulated by dynamic recruitment of Rasip1. Nature Communications, 2024; DOI: 10.1038/s41467-024-54143-y