Fruit Fly Egg Chambers Reveal Secrets of Collective Cell Movement

Scientists have long wondered how cells that are organized into sheets begin to move together to form organs, especially when the sheets form closed, sphere-like surfaces and tissues with no edges to direct motion. Researchers at the University of Chicago and UC San Diego working on this problem recently used a combination of live imaging, genetic experiments, and mathematical modeling to understand how cells in the fruit fly egg chamber synchronize movement with each other.

They found that cells can spontaneously organize and rotate together through a self-reinforcing mechanism where a specific protein helps individual cells align their movement. Once the cells start moving, that motion polarizes the protein to the back of the cell, which promotes further movement from the cells behind it in the same direction. The coordination of cell movements is mediated by mechanical connections between adjacent support cells and the global egg chamber geometry.

Epithelial cells that form surfaces in the body undergo collective migrations while tissues are developing, during the closing of wounds, the spread of cancers, or the constant turnover of things like your intestinal lining. But when there are closed surfaces, there are no external cues that tell the cells which way to go. So, this is a self-organized process."

Sally Horne-Badovinac, PhD, Professor of Molecular Genetics and Cell Biology, UChicago and senior author of the study

One of the challenges of studying this phenomenon in egg chambers is that it happens quickly. Scientists are typically able to keep them stable under a microscope for a short period of time and may miss crucial events. For this study, graduate student Sierra Schwabach used a trick of mixing chemicals that form something like a blood clot, which created a cushion to hold the egg chamber in place longer. This allowed her to capture images of the cells for up to 12 hours and observe the initiation of rotation.

"Before, we would see cells that were already rotating or that hadn't yet initiated rotation. So, it was a numbers game," Schwabach said. "Being able to watch tissues for hours allowed us to catch the switch-like process of initiation, so that was key."

The study, published in PNAS, also explains why the egg chamber always rotates around its long axis. Initially, this is caused by the physical forces through which the egg chamber interacts with nearby support tissues. As the egg chamber grows and becomes more oval-shaped, its own geometry helps stabilize the rotation axis. This work holds potential implications for understanding both normal development and diseases in which collective cell movement goes awry.

Horne-Badovinac emphasizes that the research was the result of the unique partnership between her lab and that of Mattia Serra, PhD, Associate Professor of Physics at UC San Diego. The two met through a scientific matchmaking workshop hosted by the Company of Biologists, a not-for-profit scientific publishing organization, to pair researchers who might not otherwise have a chance to collaborate. Serra and his graduate student, Sreejith Santhosh, provided physics and mathematical modeling expertise to help understand the cellular movement patterns Schwabach observed.

"This story happened through the combination of amazing technical innovation and imaging that Sierra employed and the mathematical modeling from Sreejith and Mattia," Horne-Badovinac said. "The imaging allowed us to see things about the initiation of this rotational migration that had never been seen before, while the modeling and the way the physicists saw the tissue made us think about the process completely differently. Those two things together really gave us tremendous insight."

Adapted from a research highlight provided by UC San Diego. The study, "Initiation of rotational collective migration in Drosophila through tissue geometry and mechanochemical feedback," was supported by the National Science Foundation, the Human Frontier Science Program, and the National Institutes of Health. Additional authors include Audrey Miller Williams and Maureen Cetera.