Seminars

One of the most intriguing questions in biology is how a single fertilized egg cell develops into an adult organism. This problem of developmental biology becomes even more fascinating if you zoom in a bit. Each of the individual cells seemingly “knows” where it should go to form the organism, without being able to see the whole. How do cells do that?

To help answer that question, we study blood vessel development. Endothelial cells form the internal “tapestry” of blood vessels and are one of the key players of blood vessel growth in the embryo and in the adult. Blood vessel growth is hardly easier to understand than embryo development, but fortunately we can simplify it even further by studying their behavior in isolation, in cell cultures. When cultured in a gel mimicking their natural environment, endothelial cells assemble into networks that resemble the embryonic blood vessel network. To find out how they can do that, we developed a simulation model based on observed behaviors of endothelial cells. This allows us to test our ideas of how cells assemble into shapes and patterns within the highly controlled environment of a computer simulation. Based on these insights we can suggest new experiments on the actual cell cultures and update our models accordingly.

In the simplest models, endothelial cells secrete a chemical that attracts surrounding cells; hence they assemble into isolated clusters, not networks. We will discuss a series of additional assumptions by which cells do assemble into blood-vessel-like networks, and even form blood vessel sprouts (angiogenesis). We will briefly discuss a series of recent extensions, including genetic regulation and cell-ECM interactions, and conclude by showing how the developmental principles identified models of blood vessel cultures apply to other embryonic phenomena.