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Organ-sculpting cells may hold clues to how cancer spreads

A new study by scientists at the University of North Carolina at Chapel Hill reveals that the cells shaping our organs may be far more mobile and coordinated than once believed. The study is in the journal Science Advances.

Using fruit flies as a model, researchers discovered that future muscle cells crawl across the surface of the developing testis and actively sculpt it into its final form. These dynamic cells don't work alone; they coordinate their movements using a communication system previously typically associated with brain development.

"While most organs are thought to be shaped by static, brick-like cells, our study highlights the powerful role of dynamic, migrating cells—and how they work together to sculpt living tissue," said Dr. Maik Bischoff, first and co-corresponding author of the study and postdoctoral researcher in the Peifer lab at UNC-Chapel Hill.

Scientists have long known that there are two major cell types involved in organ formation: relatively immobile epithelial cells (like bricks in a wall) and flexible, highly mobile mesenchymal cells. The team wanted to better understand how these migrating cells coordinate as a group to shape tissues during development. One of the study's most surprising findings is that these cells rely on a signaling molecule best known for wiring the brain. That insight suggests that vastly different organs, like the brain and the testis, may use similar systems to shape themselves.

They focused on the testis in developing fruit flies, which begins as an oval but eventually twists into a spiral. The researchers found that muscle precursor cells physically crawl over the surface and later constrict around the testis, shaping it from the outside. Live imaging allowed them to watch this process in real time, a significant advancement over the static tissue snapshots used in most past studies.

"If we want to understand how organs form, we have to watch the process as it happens," said Bischoff. "Trying to figure it out from static images is like learning the rules of basketball from a handful of screenshots—you miss the whole choreography."

The work has far-reaching implications. Understanding how mobile cells coordinate to mold tissues could offer new insights into how organs form and what can go wrong with developmental disorders. Due to cancer cells being another example of mesenchymal cells, studying how these cells move and communicate could also help scientists learn how tumors grow and spread.

"Mesenchymal cells are often overlooked in organ development, but they're incredibly dynamic and influential," said Dr. Mark Peifer, senior and co-corresponding author, professor of biology and member of the Lineberger Comprehensive Cancer Center at UNC-Chapel Hill. "By watching them live, we're uncovering how cells communicate and cooperate to build complex structures—and what happens when that goes wrong."

The research team also included Jenevieve Norton and Sarah Clark, postbaccalaureate researchers in the Peifer lab.