Why do cells move in the same direction together?

When cells migrate, they do so collectively. This is why Drosophila eggs rotate, for example. Here a 3D reconstruction can be seen of rotating Drosophila eggs.
© Sven Bogdan

Project title: Rotational motion in epithelial morphogenesis: Analysis of conserved molecular mechanisms
Principal investigators: Sven Bogdan, Klaus Ebnet
Project time: 07/2016 - 06/2018
Project code: FF-2016-01

When cells move, they often move as a collective. Such collective cell migration behaviour can also be observed in developing follicular cells of the Drosophila fruit fly. This collective migration leads to rotational motion along the later axis of the body. The egg rotates either clockwise or counterclockwise. But what coordinates the cells? How do they all manage to rotate clockwise or counterclockwise together? And why is the rotation in the developing egg important? Even today, the mechanisms behind this are not well understood. In this CiM project, research groups led by the biologists Prof. Dr. Sven Bogdan and Prof. Dr. Klaus Ebnet aim to achieve a more precise understanding of the rotational motion and the underlying collective cell migration. They suspect that there is an evolutionarily conserved core mechanism which leads to collective cells migration and which controls such rotational motion. Independently from one another, the researchers have observed that cells behave in a similar way in two entirely different situations: epithelial spheroids, so-called cysts, generated in 3D cell culture rotate in a three-dimensional collagen gel very similar to eggs of the fruit fly eggs during early oogenesis.  

Sven Bogdan is using Drosophila for his research. He has already discovered conserved proteins which regulate the rotational motion of developing fruit flies’ eggs. During the maturing process the eggs rotate in an egg chamber, and always vertically to the longitudinal axis. It is of no relevance whether they rotate clockwise or counterclockwise. The only thing that is decisive is that eggs rotate, because this gives rise to an extracellular, polarized matrix as a result of follicle cells which enclose the egg chamber. This matrix is a protein structure, which surrounds the cells. It functions like a corset, giving the originally round egg its typically oval form. If the eggs remain round, the fruit fly is sterile (round egg phenotype). Bogdan’s question now is: Are there similar processes in mammals?

This is where Klaus Ebnet’s group comes in. By growing human cells in a 3D collagen gel, the group generates a situation that is similar to the situation of the egg chamber in the fruit fly. From epithelial cells taken from the kidney or the breast they produce a cyst – a spherical body in which a cavity filled with fluid is surrounded by epithelial cells. Similar to the follicular cells, the epithelial cells migrate collectively, which results in a rotational motion of the entire cyst. In this experiment, as a result of the rotation, epithelial cells also form a corset of actin and myosin filaments, as in the muscle. This corset can stretch and contract. These contractions of artificially produced cysts might likewise be important for the understanding of how tubular tissues such as lung and kidney epithelia adopt shape. 

In this CiM project, Sven Bogdan and Klaus Ebnet want to study how similar or how different both processes are, and whether conserved regulators are necessary for the rotational motion. The focus of the project is on gaining a better understanding of the precise function of rotational motion in the shaping of tissue during development.