Picture the way commuters navigate a crowded subway station. “People need to be aware of where they are on multiple levels,” says Jennifer Zallen, a developmental biologist at Memorial Sloan Kettering who in May was elected a Howard Hughes Medical Institute Investigator, a highly prestigious title she shares with seven other MSK researchers. “They need to have an idea of where they’re going, but at the same time, they need to pay attention to the people immediately around them and the movements of people through the station, and adjust their course accordingly.”
Similarly, Dr. Zallen says, the cells within a developing animal are capable of sensing where they are in the body and where they need to end up to do their job — whether their intended function is to help build heart muscle or become a hair follicle. While making their way to that destination, they engage in social dynamics that coordinate their movements with neighboring cells.
Watching Fly Embryos Transform
Dr. Zallen’s lab conducts experiments in embryos of the fruit fly Drosophila melanogaster to study a particularly dramatic example of coordinated cell movement called convergent extension. In this process, a three-hour-old, blob-shaped embryo rapidly elongates to form an axis with distinct head and tail ends — a first step in shaping the fly body. This transformation, in which the embryo more than doubles in length, happens as thousands of cells nimbly reposition themselves, as if following a carefully choreographed script.
Dr. Zallen and her lab members — who combine diverse areas of expertise including biology, physics, engineering, and computer science — were able to illuminate the process using a combination of high-resolution live imaging and quantitative analysis. They created the movie clip above, which shows how the elongation happens. It begins with small groups of cells forming pinwheel-shaped clusters or rosettes. Then, in a kaleidoscopic reordering, the rosette structures expand along the embryo’s head-to-tail axis, helping to push the embryo’s head away from its rear.
The researchers found that cells communicate with one another during convergent extension not only by sending and receiving chemical signals but also by using mechanical cues that are triggered by moving cells pushing and pulling on their neighbors and traveling as sound waves through the tissue. “Mechanical signals have the potential to travel faster and farther than chemical signals in biological tissues,” Dr. Zallen says, “and could provide a mechanism to rapidly influence many cells.”Back to top
Her lab has identified a number of genes — many of which have been linked to human cancer — that play a critical role in the embryo’s elongation. Other researchers have found that in some cancer types, including breast cancer, tumor cells employ mechanisms similar to those driving convergent extension to break off from a tumor and invade the surrounding tissue.
Dr. Zallen’s lab now plans to shift their efforts to mouse models to explore how cell movements that take place early in development affect the formation of the spinal cord, and how failures in this process can lead to birth defects. “Ultimately,” she says, “the goal of our research is to understand human disease as well as to answer some of the most basic questions in biology: How do you go from individual cells to a tissue, and from individual tissues to an animal?”Back to top